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Sample records for experimentally induced myocardial

  1. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

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    Sudhira Begum

    2007-12-01

    Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

  2. Effect of Glucocorticoids on Ultrastructure of Myocardial Muscle in the Course of Experimentally Induced Acute Myocardial Ischemia

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    Piotr Kuropka

    2017-01-01

    Full Text Available The search for effective methods of myocardial cytoprotection against ischemia is the most significant issue in modern cardiology and cardiac surgery. Glucocorticoids are deemed very strong modulators of inflammatory response and thus can potentially protect heart muscle from postreperfusion injury and myocardial ischemia during cardiac surgery. Ultrastructural examination of the left ventricle heart samples revealed that the intravenous application of dexamethasone and hydrocortisone proved to exert cytoprotective effect on cardiomyocytes during experimentally induced acute ischemia in rats.

  3. Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

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    Mohanty, Ipseeta; Arya, Dharamvir Singh; Gupta, Suresh Kumar

    2006-01-01

    Background In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. Methods Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. Results Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. Conclusion In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance. PMID:16504000

  4. Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

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    Michael Lichtenauer

    Full Text Available RATIONALE: Acute myocardial infarction (AMI followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. OBJECTIVE: Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG was evaluated in this study. METHODS AND RESULTS: AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01. Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. CONCLUSIONS: These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.

  5. A synergistic protective effect of selenium and taurine against experimentally induced myocardial infarction in rats.

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    Dallak, Mohammad

    2017-12-01

    This study investigated the protective effect of subacute pre-adminsitration of either selenium (Se), taurine (Tau), or both drugs in combination against experimentally induced myocardial infarction (MI) in rats and illustrates the possible mechanisms of action. While solely pre-administration of Se or Tau resulted in partial amelioration in all of the measured parameters in MI rats, concomitant administration of both drugs to MI rats significantly restored contractility function by increasing LVSP and decreasing LVEDP and significantly normalized serum levels of LDH, CK-MB and BNP and restored normal cardiac architecture. This concomitant treatment acted by increasing the activity of major antioxidant enzymes (SOD and GPx), decreasing the levels of inflammatory markers including TNF-α, IL-6 as well as levels of Bcl-2 and caspase-3 and downregulating mRNA levels of Bax and P53, markers of apoptosis. In conclusion, a combination of Se and Tau provides a new strategy to alleviate MI-induced cardiac dysfunction.

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

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    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

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

  7. INFLAMMATORY REACTIONS IN EXPERIMENTAL MYOCARDIAL DAMAGE

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    L. D. Khidirova

    2015-12-01

    Full Text Available Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80 were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days. Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml. Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.

  8. INFLAMMATORY REACTIONS IN EXPERIMENTAL MYOCARDIAL DAMAGE

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    L. D. Khidirova

    2012-01-01

    Full Text Available Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80 were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days. Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml. Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.

  9. [Bonsai induced acute myocardial infarction].

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    Ayhan, Hüseyin; Aslan, Abdullah Nabi; Süygün, Hakan; Durmaz, Tahir

    2014-09-01

    Incidences of drug abuse and cannabis have increased in young adults, recently. Cannabis induced myocardial infarction has rarely been reported in these people. There is no any literature about a synthetic cannabinoid, being recently most popular Bonsai, to cause myocardial infarction. In this case report we presented a 33-year-old male patient who developed acute myocardial infarction after taking high doses of Bonsai.

  10. Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

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    Chorro, Francisco J; Canto, Irene Del; Brines, Laia; Such-Miquel, Luis; Calvo, Conrado; Soler, Carlos; Zarzoso, Manuel; Trapero, Isabel; Tormos, Álvaro; Such, Luis

    2015-12-01

    Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 μM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 μM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 μM, n = 9). EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [P<.001]). During stretch, the activation maps were less complex (P<.0001) and the spectral concentration of the arrhythmia was greater (greater regularity) in the EIPA series: control=18 (3%); EIPA = 26 (9%) (P < .02); losartan=18 (5%) (not significant); and BQ-123=18 (4%) (not significant). The Na(+)/H(+) exchanger inhibitor EIPA attenuated the electrophysiological effects responsible for the acceleration and increased complexity of ventricular fibrillation induced by acute myocardial stretch. The angiotensin II receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

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    Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

    2008-12-01

    To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

  12. Effect of melatonin on myocardial oxidative stress induced by experimental obstructive jaundice Efecto de la melatonina en el estrés oxidativo del miocardio en un modelo experimental de obstrucción biliar

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    A. Cruz

    2009-07-01

    Full Text Available Objective: melatonin has been demonstrated to have active antioxidant properties in different tissues during experimental cholestasis. The aim of this research was to study myocardial oxidative stress on obstructive jaundice, and to analyze the effect of melatonin on myocardial oxidative lesions. Material and methods: we achieved cholestasis by ligature and sectioning of the main bile duct. Melatonin was administered intraperitoneally (500 µg/kg/day. We measured malondialdehyde (MDA, reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD and glutathione peroxydase (GPx antioxidant enzyme levels in the heart tissue. Results: obstructive cholestasis increased MDA and decreased GSH as well as all antioxidant enzymes. Melatonin administration significantly decreased MDA values, and increased GSH and antioxidant enzymes on the icteric animal myocardium. Conclusions: melatonin treatment prevents oxidative stress in the cardiac tissue as induced by experimental cholestasis.

  13. Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos Experimental model of myocardial infarction induced by isoproterenol in rats

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    Heraldo Guedis Lobo Filho

    2011-09-01

    Full Text Available OBJETIVO: Avaliar e validar, em nosso meio, o modelo de infarto do miocárdio induzido por isoproterenol em ratos por meio de análises de parâmetros hematológicos, bioquímicos, de marcadores do estresse oxidativo e histopatológicos. MÉTODOS: Trinta ratos jovens, machos, da linhagem Wistar (145 a 230 g, foram alocados aleatoriamente em dois grupos: grupo Simulado, submetido à falsa indução de infarto do miocárdio, e grupo Infarto, submetido à indução do infarto do miocárdio com isoproterenol. As aplicações, para indução do infarto, foram realizadas durante dois dias consecutivos, com intervalo de 24 horas entre elas. Após 24 horas da última aplicação, os ratos de ambos os grupos foram anestesiados e sacrificados para realização de coleta de sangue para hemograma e análise bioquímica (TGO, TGP, troponina I, ureia e creatinina e coleta de fragmento do miocárdio para avaliação de marcadores do estresse oxidativo (atividade da catalase e concentração de glutationa e exame histopatológico. RESULTADOS: Não houve mortalidade no grupo Simulado, enquanto a mortalidade no grupo Infarto foi de 25%. A indução do infarto do miocárdio com isoproterenol causou elevação das contagens de leucócitos e neutrófilos, dos níveis de TGO, troponina I e ureia, reduziu a atividade da catalase e os níveis teciduais de glutationa e causou alterações histopatológicas. Não acarretou alterações nas concentrações de hemoglobina, TGP e creatinina. CONCLUSÕES: O modelo de infarto do miocárdio induzido por isoproterenol em ratos foi adequadamente reproduzido em nosso laboratório, acarretando alterações em parâmetros hematológicos, bioquímicos, de marcadores de estresse oxidativo e histopatológicos.OBJECTIVE: To evaluate and validate, in our laboratory, the essay of myocardial infarction induced by isoproterenol in rats by means of analysis of hematological, biochemical, oxidative stress markers and histopathological

  14. Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43.

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    Miriam Kalbitz

    Full Text Available Severe blunt chest trauma in humans is associated with high mortality rates. Whereas lung tissue damage and lung inflammation after blunt chest trauma have extensively been investigated, the traumatic and posttraumatic effects on the heart remain poorly understood. Therefore, the purpose of this study was to define cardiac injury patterns in an experimental blunt chest trauma model in rats.Experimental blunt chest trauma was induced by a blast wave in rats, with subsequent analysis of its effects on the heart. The animals were subjected either to a sham or trauma procedure. Systemic markers for cardiac injury were determined after 24 h and 5 days. Postmortem analysis of heart tissue addressed structural injury and inflammation 24 h and 5 days after trauma.Plasma levels of extracellular histones were elevated 24 h and 5 days after blunt chest trauma compared to sham-treated animals. In the heart, up-regulation of interleukin-1β 24 h after trauma and increased myeloperoxidase activity 24 h and 5 days after trauma were accompanied by reduced complement C5a receptor-1 expression 24 h after trauma. Histological analysis revealed extravasation of erythrocytes and immunohistochemical analysis alteration of the pattern of the gap-junction protein connexin 43. Furthermore, a slight reduction of α-actinin and desmin expression in cardiac tissue was found after trauma together with a minor increase in sarcoplasmatic/endoplasmatic reticlulum calcium-ATPase (SERCA expression.The clinically highly relevant rat model of blast wave-induced blunt chest trauma is associated with cardiac inflammation and structural alterations in cardiac tissue.

  15. Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43.

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    Kalbitz, Miriam; Amann, Elisa Maria; Bosch, Belinda; Palmer, Annette; Schultze, Anke; Pressmar, Jochen; Weber, Birte; Wepler, Martin; Gebhard, Florian; Schrezenmeier, Hubert; Brenner, Rolf; Huber-Lang, Markus

    2017-01-01

    Severe blunt chest trauma in humans is associated with high mortality rates. Whereas lung tissue damage and lung inflammation after blunt chest trauma have extensively been investigated, the traumatic and posttraumatic effects on the heart remain poorly understood. Therefore, the purpose of this study was to define cardiac injury patterns in an experimental blunt chest trauma model in rats. Experimental blunt chest trauma was induced by a blast wave in rats, with subsequent analysis of its effects on the heart. The animals were subjected either to a sham or trauma procedure. Systemic markers for cardiac injury were determined after 24 h and 5 days. Postmortem analysis of heart tissue addressed structural injury and inflammation 24 h and 5 days after trauma. Plasma levels of extracellular histones were elevated 24 h and 5 days after blunt chest trauma compared to sham-treated animals. In the heart, up-regulation of interleukin-1β 24 h after trauma and increased myeloperoxidase activity 24 h and 5 days after trauma were accompanied by reduced complement C5a receptor-1 expression 24 h after trauma. Histological analysis revealed extravasation of erythrocytes and immunohistochemical analysis alteration of the pattern of the gap-junction protein connexin 43. Furthermore, a slight reduction of α-actinin and desmin expression in cardiac tissue was found after trauma together with a minor increase in sarcoplasmatic/endoplasmatic reticlulum calcium-ATPase (SERCA) expression. The clinically highly relevant rat model of blast wave-induced blunt chest trauma is associated with cardiac inflammation and structural alterations in cardiac tissue.

  16. Overexpression myocardial inducible nitric oxide synthase exacerbates cardiac dysfunction and beta-adrenergic desensitization in experimental hypothyroidism.

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    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2016-02-01

    Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca(2+)]i transient ([Ca(2+)]iT), and β-adrenergic hyporesponsiveness. We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca(2+)]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400 W, 10(-5)mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca(2+)]iT. In hypothyroidism, isoproterenol (10(-8)M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca(2+)]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca(2+)]iT. Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cardiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. Copyright © 2015 Elsevier

  17. Overexpression Myocardial Inducible Nitric Oxide Synthase Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in Experimental Hypothyroidism☆,☆☆

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    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F.; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2015-01-01

    Background Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cadiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca2+]i transient ([Ca2+]iT), and β-adrenergic hyporesponsiveness. Methods and Results We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca2+]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400W, 10−5 mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. In hypothyroidism, isoproterenol (10−8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca2+]iT. Conclusions Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cadiomyocyte iNOS may promote progressive cardiac dysfunction in

  18. Catecholamine-Induced Myocardial Damage Associated with ...

    African Journals Online (AJOL)

    Four out of 7 patients dying of phaeochromocytomas and 7 out of 11 dying of tetanus had microscopic widespread myofibre damage (myofibrillar degeneration and 'myocytolysis). It is suggested that the myocardial lesions in both groups are induced by catecholamine excess. In those with phaeochromocytomas the ...

  19. Increases in myeloperoxidase levels after exercise in myocardial perfusion scintigraphy are not induced by myocardial ischemia

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    van der Zee, P. M.; Meuwese, M. C.; Verberne, H. J.; de Ruijter, M.; van Straalen, J. P.; Fischer, J. C.; Sturk, A.; van Eck-Smit, B. L. F.; Stroes, E. S. G.; de Winter, R. J.

    2008-01-01

    Background: Increased systemic levels of myeloperoxidase (MPO) have been reported in patients with acute myocardial ischemia. We studied the association between exercise-induced myocardial ischemia measured by myocardial perfusion scintigraphy (MPS) and the magnitude and time course of changes in

  20. Experimental Myocardial Infarction: The quest for novel therapeutics

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    Hout, G.P.J. van

    2015-01-01

    Myocardial infarction (MI) and its consequences are associated with high mortality rates and considerable health care costs. Novel therapeutics that protect the heart after MI are therefore required. To assess safety and efficacy before exposing patients to experimental compounds, thorough

  1. Metformin protects against infection-induced myocardial dysfunction

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    Tzanavari, Theodora; Varela, Aimilia; Theocharis, Stamatis; Ninou, Elpinickie; Kapelouzou, Alkistis; Cokkinos, Dennis V.; Kontaridis, Maria I.; Karalis, Katia P.

    2017-01-01

    Background and Purpose Metformin administration is associated with myocardial protection during ischemia and/or reperfusion, possibly via inhibition of inflammatory responses in the heart. Exposure to pathogens, in addition to the activation of the immune system and the associated metabolic dysfunction, often results in compromised myocardial function. We examined whether metformin administration could maintain the normal myocardial function in experimental moderate Gram negative infection, induced by lipopolysaccharide (LPS) administration. Experimental Approach 129xC57BL/6 mice were divided into control groups that received either vehicle or a single intraperitoneal (i.p.) injection of low dose LPS (5 mg/kg body wt), and metformin treated groups that received either daily metformin (4 mg/kg/animal) i.p. injections for five days prior to LPS administration [Experiment 1], or a single metformin injection following same dose of LPS [Experiment 2]. Key Results LPS alone caused cardiac dysfunction, as confirmed by echocardiography, whereas metformin administration, either before or after LPS, rescued myocardial function. LPS caused marked reduction of the cardiac metabolism-related genes tested, including Prkaa2, Cpt1b, Ppargc1a and Ppargc1b; reduction of fatty acid oxidation, as reflected by the regulation of Ppara, Acaca and Acacb; increased glucose transport, as shown by Slc2a4 levels; reduction of ATP synthesis; significant increase of inflammatory markers, in particular IL6; and reduction of autophagy. Pretreatment with metformin normalized the levels of all these factors. Conclusions and Implications We show for the first time that metformin protects the myocardium from LPS-associated myocardial dysfunction mainly by supporting its metabolic activity and allowing efficient energy utilization. Metformin can be a potential cardioprotective agent in individuals susceptible to exposure to pathogens. PMID:27621180

  2. Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies

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    Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

    2006-01-01

    Objective To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Methods and results Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2  =  0.92 versus r2  =  0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (κ  =  0.87 v κ  =  0.75, p < 0.05). Conclusion MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine. PMID:15939722

  3. delta-Opioid-induced pharmacologic myocardial hibernation during cardiopulmonary resuscitation.

    Science.gov (United States)

    Fang, Xiangshao; Tang, Wanchun; Sun, Shijie; Weil, Max Harry

    2006-12-01

    Cardiac arrest and cardiopulmonary resuscitation is an event of global myocardial ischemia and reperfusion, which is associated with severe postresuscitation myocardial dysfunction and fatal outcome. Evidence has demonstrated that mammalian hibernation is triggered by cyclic variation of a delta-opiate-like compound in endogenous serum, during which the myocardial metabolism is dramatically reduced and the myocardium tolerates the stress of ischemia and reperfusion without overt ischemic and reperfusion injury. Previous investigations also proved that the delta-opioid agonist elicited the cardioprotection in a model of regional ischemic intact heart or myocyte. Accordingly, we were prompted to search for an alternative intervention of pharmacologically induced myocardial hibernation that would result in rapid reductions of myocardial metabolism and therefore minimize the myocardial ischemic and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation. Prospective, controlled laboratory study. University-affiliated research laboratory. In the series of studies performed in the established rat and pig model of cardiac arrest and cardiopulmonary resuscitation, the delta-opioid receptor agonist, pentazocine, was administered during ventricular fibrillation. : The myocardial metabolism reflected by the concentration of lactate, or myocardial tissue PCO2 and PO2, is dramatically reduced during cardiac arrest and cardiopulmonary resuscitation. These are associated with less severe postresuscitation myocardial dysfunction and longer duration of postresuscitation survival. delta-Opioid-induced pharmacologic myocardial hibernation is an option to minimize the myocardial ischemia and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation.

  4. Chest Pain and Mental Stress-Induced Myocardial Ischemia: Sex Differences.

    Science.gov (United States)

    Pimple, Pratik; Hammadah, Muhammad; Wilmot, Kobina; Ramadan, Ronnie; Al Mheid, Ibhar; Levantsevych, Oleksiy; Sullivan, Samaah; Garcia, Ernest V; Nye, Jonathon; Shah, Amit J; Ward, Laura; Mehta, Puja; Raggi, Paolo; Bremner, J Douglas; Quyyumi, Arshed A; Vaccarino, Viola

    2017-12-07

    Mental stress-induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease. Women with coronary artery disease tend to have more mental stress-induced myocardial ischemia and more chest pain/anginal symptoms than men, but whether the association between mental stress-induced myocardial ischemia and angina burden differs in women and men is unknown. This was a cross-sectional study with experimental manipulation of 950 individuals with stable coronary artery disease. Chest pain/angina frequency in the previous 4 weeks was assessed with the Seattle Angina Questionnaire's angina-frequency subscale. Mental stress-induced myocardial ischemia was assessed with myocardial perfusion imaging during mental stress (standardized public speaking task). Presence of mental stress-induced myocardial ischemia was based on expert readers and established criteria. A conventional (exercise or pharmacologic) stress test was used as a control condition. Overall, 338 individuals (37%) reported angina; 112 (12%) developed mental stress-induced myocardial ischemia, and 256 (29%) developed conventional stress ischemia. Women who reported angina had almost double the probability to develop mental stress-induced myocardial ischemia (19% vs 10%, adjusted prevalence rate ratio, 1.90; 95% confidence interval, 1.04-3.46), whereas there was no such difference in men (11% vs 11%, adjusted prevalence rate ratio, 1.09; 95% confidence interval, 0.66-1.82). No association was found between angina symptoms and conventional stress ischemia for women or men. Results for ischemia as a continuous variable were similar. In women, but not in men, anginal symptoms may be a marker of vulnerability toward ischemia induced by psychologic stress. These results highlight the psychosocial origins of angina in women and may have important implications for the management and prognosis of women with angina. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Exercise induced ST elevation and residual myocardial ischemia in previous myocardial infarction

    International Nuclear Information System (INIS)

    Shimonagata, Tsuyoshi; Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Saito, Muneyasu; Sumiyoshi, Tetsuya

    1987-01-01

    The purpose of this study was to evaluate the clinical significance of stress induced ST elevation on infarcted area in 65 patients with previous myocardial infarction (single vessel disease) who had stress thallium scan. Stress induced ST changes on infarcted area were compared with quantitative assessment of myocardial ischemia (thallium ischemic score; TIS) and extent of myocardial infarction (defect score; DS) derived from circumferential profile analysis. In patients with previous myocardial infarction in less than 3 month from the onset (n = 36), left ventricular ejection fraction (LVEF) and extent of abnormal LV wall motion were not significantly different between patients with stress induced ST elevation ( ≥ 2 mm, n = 26) and those with stress induced ST elevation ( < 2 mm, n = 10), while, in patients with previous myocardial infarction in more than 3 month (n = 29), patients with stress induced ST elevation ( ≥ 2 mm, n = 15) showed left ventricular dyskinesis more frequently than those with ST elevation ( < 2 mm, n = 14). In addition, the former showed significantly higher DS and significantly lower TIS than the latter. In patients with previous myocardial infarction in less than 3 month, patients with ST elevation ( ≥ 2 mm, n = 15) with prominent upright T wave (n = 15) had transient thallium defect in infarcted area in 73 % and they had significantly higher LVEF and TIS than those with ST elevation ( < 2 mm, n = 11). These results indicated that ST elevation in infarcted area reflect different significance according to the recovery of injured myocardium and stress induced ST elevation with prominent upright T wave in infarcted area reflect residual myocardial ischemia in less than 3 month from the onset of myocardial infarction. (author)

  6. Nitroglycerine induced acute myocardial infarction in a patient with myocardial bridging

    DEFF Research Database (Denmark)

    Rujic, Dragana; Nielsen, Mette Lundgren; Veien, Karsten Tange

    2014-01-01

    Muscle overlying an intramyocardial segment of a coronary artery is termed a myocardial bridge. The intramyocardial segment, the tunneled artery, is compressed during systole. The condition is generally benign but may occasionally cause myocardial ischemia, infarction, arrhythmia, or sudden cardiac...... death. We present a case regarding a 52-year-old man with exercise-induced angina who was diagnosed with a myocardial bridge overlying the left anterior descending artery. He was initially treated with beta-blockers and later received coronary bypass graft surgery....

  7. Experimental Myocardial Infarction: The quest for novel therapeutics

    OpenAIRE

    Hout, G.P.J. van

    2015-01-01

    Myocardial infarction (MI) and its consequences are associated with high mortality rates and considerable health care costs. Novel therapeutics that protect the heart after MI are therefore required. To assess safety and efficacy before exposing patients to experimental compounds, thorough preclinical testing in representative translational animals is required. However, successful clinical implementation of cardioprotective compounds has not yet been established, while many animal studies hav...

  8. Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats.

    Science.gov (United States)

    Li, Xiaoqing; Cheng, Qinghong; Li, Jianhua; He, Yonglai; Tian, Peigang; Xu, Chao

    2017-09-01

    Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H 2 S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H 2 S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (Panti-inflammatory cytokine and biomarker in sepsis-induced myocardial injury. Furthermore, H 2 S may downregulate the NF-κB subunit p65 to mediate inflammatory responses. The present data suggest that myocardial injury in sepsis may be relieved through the regulation of H 2 S expression, and provide an experimental basis for the treatment of sepsis patients presenting with myocardial injury. In addition, myocardial injury in sepsis may be identified by monitoring changes in the expression of H 2 S.

  9. Liraglutide-induced reduction of myocardial ischemiareperfusion ...

    African Journals Online (AJOL)

    Purpose: To investigate the protective effect of liraglutide on myocardial ischemia reperfusion (I/R) injury and its molecular mechanism. Methods: Ischemia reperfusion model male Sprague-Dawley (SD) rats were randomly divided into negative control group, I/R group (saline), liraglutide group (liraglutide) and PD group ...

  10. Myocardial atrophy and chronic mechanical unloading of the failing human heart: implications for cardiac assist device-induced myocardial recovery.

    Science.gov (United States)

    Diakos, Nikolaos A; Selzman, Craig H; Sachse, Frank B; Stehlik, Josef; Kfoury, Abdallah G; Wever-Pinzon, Omar; Catino, Anna; Alharethi, Rami; Reid, Bruce B; Miller, Dylan V; Salama, Mohamed; Zaitsev, Alexey V; Shibayama, Junko; Li, Hui; Fang, James C; Li, Dean Y; Drakos, Stavros G

    2014-10-14

    In animal models of heterotopic transplantation, mechanical unloading of the normal, nonhypertrophic heart results in atrophy. Primarily on the basis of these animal data, the notion that chronic left ventricular assist device (LVAD)-induced unloading will result in atrophy has dominated the clinical heart failure field, and anti-atrophic drugs have been used to enhance the cardiac recovery potential observed in some LVAD patients. However, whether unloading-induced atrophy in experimental normal heart models applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs has not been studied. The study examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy. We prospectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors. Cardiomyocyte size (cross-sectional area) decreased after LVAD unloading from 1,238 ± 81 μm(2) to 1,011 ± 68 μm(2) (p = 0.001), but not beyond that of normal donor hearts (682 ± 56 μm(2)). Electron microscopy ultrastructural evaluation, cardiomyocyte glycogen content, and echocardiographic assessment of myocardial mass and left ventricular function also did not suggest myocardial atrophy. Consistent with these findings, t-tubule morphology, cytoplasmic penetration, and distance from the ryanodine receptor were not indicative of ongoing atrophic remodeling during LVAD unloading. Molecular analysis revealed no up-regulation of proatrophic genes and proteins of the ubiquitin proteasome system. Structural, ultrastructural, microstructural, metabolic, molecular, and clinical functional data indicated that prolonged continuous-flow LVAD unloading does not induce hypertrophy regression to the point of atrophy and degeneration. These findings may be useful in designing future investigations that combine LVAD unloading and pharmaceutical therapies as a bridge to recovery of the failing heart

  11. Reverse 201Tl myocardial redistribution induced by coronary artery spasm

    International Nuclear Information System (INIS)

    Xiang Dingcheng; Yin Jilin; Gong Zhihua; Xie Zhenhong; Zhang Jinhe; Wen Yanfei; Yi Shaodong

    2010-01-01

    Objective: To investigate the mechanism of reverse redistribution (RR) on dipyridamole 201 Tl myocardial perfusion studies in the patients with coronary artery spasm. Methods: Twenty-six patients with coronary artery spasm and presented as RR on dipyridamole 201 Tl myocardial perfusion studies were enlisted as RR group, while other 16 patients with no coronary artery stenosis nor RR were enlisted as control group. Dipyridamole test was repeated during coronary angiography. Corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) were measured at RR related and non-RR related coronary arteries before and after dipyridamole infusion respectively. All of the data were analyzed by Student's t-test or χ 2 -test and correlation analysis. Results: Coronary artery angiography showed slower blood flow and lower myocardial perfusion in RR related vessels when compared with non-RR related vessels in RR group, but there was no significant difference among the main coronary arteries in control group. The perfusion defects of RR area at rest were positively related to slower blood velocity at corresponding coronary arteries (r = 0.79, t =10.18, P 0.05). Conclusion: RR is related to the decreased blood flow and myocardial perfusion induced by coronary artery spasm at rest, which may be improved by stress test such as intravenous dipyridamole infusion. (authors)

  12. Postoperative myocardial performance during glucose-induced hypophosphatemia

    DEFF Research Database (Denmark)

    Rasmussen, A; Buus, S; Hessov, I

    1985-01-01

    Long-lasting hypophosphatemia was previously found to diminish myocardial performance. The present study aimed to elucidate if postoperative glucose-induced hypophosphatemia is of importance for myocardial performance. Sixteen patients undergoing elective colonic or rectal surgery were given 100 g...... glucose intravenously (as 20% glucose solution) on the first and second postoperative days. The infusion rate was 0.3 g/kg/hour. On both days the glucose infusion caused significant fall in P-phosphate (0.94 to 0.67 and 0.71 to 0.47 mmol/l, respectively). No changes were seen in P-calcium, P-potassium....... As the preload (central venous pressure) and the afterload (arterial pressure) similarly were unchanged by the glucose infusion, glucose-induced hypophosphatemia following elective surgery was judged to lack importance for the myocardial performance....

  13. Induction of a chronic myocardial infarction in the laboratory animal - experimental model

    Science.gov (United States)

    POP, IONEL CIPRIAN; GRAD, NICOLAE-OVIDIU; PESTEAN, COSMIN; TAULESCU, MARIAN; MIRCEAN, MIRCEA; MIRONIUC, ION-AUREL

    2013-01-01

    Introduction Ischemic heart disease is a major public health problem in western countries. Appropriate animal experimental models of chronic myocardial infarction is an essential first step in order to investigate and develop new therapeutic interventions. Aim The aim of this study was to find an optimal place for a coronary artery ligation to induce an optimal chronic myocardial infarction and also a new heart approach that will not require oro-tracheal intubation. Material and methods To achieve these goals we used a group of rabbits and after induction of anesthesia and cardiac exposure by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side we performed three different left anterior descending artery (LAD) ligation at different distances (5, 10 and 15 mm) in relation to the apex. Thirty days after the acute myocardial infarction, we correlated laboratory investigations (serology, ECG, cardiac ultrasound) with histopathological findings. Results Heart approach achieved by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side, maintains the integrity of the ribcage, allowing it to take part in respiratory movements and the animal model does not need oro-tracheal intubation. Ligation of LAD at 15 mm from the apex was incompatible with life; ligation of LAD at 5 mm from the apex does not achieved transmural myocardial infarction and ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle which also involved the distal part of the interventricular septum. Conclusion Ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle, is in an easily accessible area from technical point of view, it is sufficiently expanded to induce hemodynamic effects that can be quantified with paraclinical examination and also it is compatible with the experimental animal life. If the heart is approached by rib III, IV and V

  14. Protective effect of catalpol on isoproterenol-induced myocardial ...

    African Journals Online (AJOL)

    hope&shola

    2012-05-10

    May 10, 2012 ... The neuroprotective effects of catalpol had been well demonstrated in many studies. Nevertheless, little work was done to investigate the cardioprotective effects of catalpol. This study was designed to explore whether catalpol protected myocardium against isoproterenol (ISO)-induced myocardial injury.

  15. Protective effect of catalpol on isoproterenol-induced myocardial ...

    African Journals Online (AJOL)

    hope&shola

    2012-05-10

    May 10, 2012 ... This study was designed to explore whether catalpol protected myocardium against isoproterenol (ISO)-induced myocardial injury ... expressions of tumor necrosis factor-a (TNF-a) and interleukin-1β (IL-1β) caused by ISO. In conclusion, .... muscle fibres without any necrosis (Figure 1A). The morphology of ...

  16. Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats.

    Science.gov (United States)

    Lobo, Reema Orison; Shenoy, Chandrakala K

    2015-07-01

    Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed.

  17. Sepsis-Induced Myocardial Depression and Takotsubo Syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Kemal Arslantaş

    2015-08-01

    Full Text Available Sepsis induced temporary myocardial dysfunction characterized as impairment of myocardial contraction is an important cause of mortality and morbidity in intensive care units. Takotsubo syndrome (TS is temporary ballooning and dysfunction of the apical part of left ventricle without significant stenosis of coronary arteries. Recently, it was suggested that impairment in regional catecholamine distribution caused by stress factors and excessive cardiac sympathetic activity mechanism play role in sepsis such as other causes of TS. Additionally, vasopressor agents (as noradrenaline which are widely used in sepsis treatment may be triggering factor. Serial case reports of sepsis associated TS are reported, however pathophysiology, diagnosis and treatment strategies of these two different syndromes is not obvious.

  18. Protective effect of squalene on certain lysosomal hydrolases and free amino acids in isoprenaline-induced myocardial infarction in rats

    DEFF Research Database (Denmark)

    Farvin, Sabeena; Surendraraj, A.; Anandan, R.

    2010-01-01

    This study was aimed to evaluate the preventive role of squalene on free amino acids and lysosomal alterations in experimentally induced myocardial infarction in rats. The levels of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, beta-glucosidase, acid phosphatase and cathepsin D) in p...

  19. Myocardial glucose uptake and breakdown during adenosine-induced vasodilation.

    Science.gov (United States)

    Turnheim, K; Donath, R; Weissel, M; Kolassa, N

    1976-09-30

    In isolated K+ (16.2 mM)-arrested cat hearts perfused at constant pressure adenosine infusions (0.8 mumoles - min-1 - 100 g-1 for 10 min) caused an increase in myocardial 14C-glucose uptake and release of 14CO2 + H14CO3- AND 14C-lactate simultaneously with a rise in coronary flow. The ratio of the release of 14CO2 + H14CO3- to that of 14C-lactate and the specific activity of lactate in the effuate were not altered. In K+ -arrested hearts perfused with constant volume neither glucose uptake nor glucose breakdown were influenced by 0.8 or 100 mumoles - min-1 - 100 g-1 adenosine with 0.1 - 5 mM glucose in the perfusion medium. It is concluded that adenosine does not affect directly the myocardial glucose carrier system, aerobic or anaerobic glucose breakdown or glycogenolysis, but enhances glucose uptake secondarily by increasing coronary flow. This interpretation is substantiated by the finding that mechanically produced increases in perfusion volume caused similar increases in myocardial glucose uptake as were observed with comparable adenosine-induced coronary flow increments.

  20. Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

    Directory of Open Access Journals (Sweden)

    Weytjens Caroline

    2008-09-01

    Full Text Available Abstract The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with Streptozotocin-induced diabetic rats using contrast echocardiography. Methods We prospectively studied 40 Wistar rats. Diabetes was induced by intravenous streptozotocin in 20 rats. All rats underwent baseline and stress (dipyridamole: 20 mg/kg high power intermittent imaging in short axis view under anaesthesia baseline and after six months. Myocardial blood flow was determined and compared at rest and after dipyridamole in both populations. The myocardial blood flow reserve was calculated and compared in the 2 groups. Parameters of left ventricular function were determined from the M-mode tracings and histological examination was performed in all rats at the end of the study. Results At six months, myocardial blood flow reserve was significantly lower in diabetic rats compared to controls (3.09 ± 0.98 vs. 1.28 ± 0.67 ml min-1 g-1; p Conclusion In this animal study, diabetes induced a functional alteration of the coronary microcirculation, as demonstrated by contrast echocardiography, a decrease in capillary density and of the cardiac systolic function. These findings may offer new insights into the underlying mechanisms of diabetes cardiomyopathy.

  1. High fat diet-induced glucose intolerance impairs myocardial function, but not myocardial perfusion during hyperaemia: a pilot study

    Directory of Open Access Journals (Sweden)

    van den Brom Charissa E

    2012-06-01

    Full Text Available Abstract Background Glucose intolerance is a major health problem and is associated with increased risk of progression to type 2 diabetes mellitus and cardiovascular disease. However, whether glucose intolerance is related to impaired myocardial perfusion is not known. The purpose of the present study was to study the effect of diet-induced glucose intolerance on myocardial function and perfusion during baseline and pharmacological induced hyperaemia. Methods Male Wistar rats were randomly exposed to a high fat diet (HFD or control diet (CD (n = 8 per group. After 4 weeks, rats underwent an oral glucose tolerance test. Subsequently, rats underwent (contrast echocardiography to determine myocardial function and perfusion during baseline and dipyridamole-induced hyperaemia (20 mg/kg for 10 min. Results Four weeks of HFD feeding resulted in glucose intolerance compared to CD-feeding. Contractile function as represented by fractional shortening was not altered in HFD-fed rats compared to CD-fed rats under baseline conditions. However, dipyridamole increased fractional shortening in CD-fed rats, but not in HFD-fed rats. Basal myocardial perfusion, as measured by estimate of perfusion, was similar in CD- and HFD-fed rats, whereas dipyridamole increased estimate of perfusion in CD-fed rats, but not in HFD-fed rats. However, flow reserve was not different between CD- and HFD-fed rats. Conclusions Diet-induced glucose intolerance is associated with impaired myocardial function during conditions of hyperaemia, but myocardial perfusion is maintained. These findings may result in new insights into the effect of glucose intolerance on myocardial function and perfusion during hyperaemia.

  2. Cardioprotective effect of Azadirachta indica A. Juss. on isoprenaline induced myocardial infarction in rats.

    Science.gov (United States)

    Peer, Prashee A; Trivedi, Purvi C; Nigade, Prashant B; Ghaisas, Mahesh M; Deshpande, Avinash D

    2008-05-07

    The present study was designed to evaluate the cardioprotective potential of aqueous leaf extract of Azadirachta indica A. Juss. (AI) on the basis of haemodynamic, biochemical and histopathological parameters in isoprenaline induced myocardial infarction in rats and to compare with vitamin E, a known cardioprotective antioxidant. A significant (plevel of cardiac marker enzymes [Lactate dehydrogenase (LDH) and Serum Glutamate Oxalotransaminase (SGOT)] in the heart homogenate with a corresponding increase in their level in serum. In vitamin E control group significant (plevels while decrease in high-density lipoproteins (HDL) was observed. On histopathological examination, myocardial damage in isoprenaline control group further confirmed cardiotoxic effect of isoprenaline. Our data showed that AI (250, 500 and 1000 mg/kg, p.o.) and vitamin E (100 mg/kg, p.o.) significantly restores most of the haemodynamic, biochemical and histopathalogical parameters. Finally we concluded that AI leaf extract exerts equipotent cardioprotective activity in the experimental model of isoprenalin induced myocardial necrosis in rats as compared to vitamin E, a known cardioprotective antioxidant.

  3. Imaging of cocaine-induced global and regional myocardial ischemia

    International Nuclear Information System (INIS)

    Oster, Z.H.; Som, P.; Wang, G.J.; Weber, D.A.

    1991-01-01

    Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. The authors have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine

  4. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja D.; Qayyum, Abbas A.

    2016-01-01

    Ischemic heart disease (IHD) is one of the leading causes of death worldwide and is characterized by the formation of atherosclerotic plaques in the coronary arteries reducing the blood supply to the heart muscle causing ischemia. IHD can result in ST-elevation myocardial infarction (STEMI...... interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct...

  5. Imaging experimental myocardial infarction with indium-111-labeled autologous leukocytes: effects of infarct age and residual regional myocardial blood flow

    International Nuclear Information System (INIS)

    Thakur, M.L.; Gottschalk, A.; Zaret, B.L.

    1979-01-01

    The external imaging patterns and the kinetics of infiltration of indium-111 labeled polymorphonuclear leukocytes (PMNs) occurring in the course of the inflammatory response associated with myocardial infarction were studied in dogs subjected to closed-chest anterior wall infarction. The effects of infarct age and regional residual myocardial blood flow upon PMN infiltration were investigated and quantified, and the capacity of indium-111 PMNs to image the experimental infarction was evaluated qualitatively. The epicardial accumulation of indium-111 PMNs occurred primarily in infarct zones with residual blood flow of 0.6 times normal and was maximal (14.8 +- 3.8 times normal) in the lowest blood flow zone (< 0.1 times normal). PMN accumulation in the endocardial infarct zones occurred in the regions with blood flow < 0.6 times normal and was maximal (26.8 +- 4.9 times normal) in the lowest blood flow zone. However, contrary to the maximal epicardial infiltration period, which occurred within the first 24 h after infarction, the maximal endocardial infiltration occurred at 72 hours after infarction. In both endocardium and epicardium, PMN uptake was minimal at 120 h after infarction. In vivo cardiac images were abnomal and revealed discrete, anatomically distinct areas of increased myocardial radioactivity uptake in the anterior wall of all dogs studied within 24 to 96 h after infarction. All images obtained 120 h after infarction were negative. Thus, indium-111 PMNs provide a noninvasive means of in vivo imaging of the inflammatory response to myocardial infarction and allow quantification of this response at a tissue level

  6. TNF-Like Weak Inducer of Apoptosis Aggravates Left Ventricular Dysfunction after Myocardial Infarction in Mice

    Directory of Open Access Journals (Sweden)

    Kai-Uwe Jarr

    2014-01-01

    Full Text Available Background. TNF-like weak inducer of apoptosis (TWEAK has recently been shown to be potentially involved in adverse cardiac remodeling. However, neither the exact role of TWEAK itself nor of its receptor Fn14 in this setting is known. Aim of the Study. To analyze the effects of sTWEAK on myocardial function and gene expression in response to experimental myocardial infarction in mice. Results. TWEAK directly suppressed the expression of PGC-1α and genes of oxidative phosphorylation (OXPHOS in cardiomyocytes. Systemic sTWEAK application after MI resulted in reduced left ventricular function and increased mortality without changes in interstitial fibrosis or infarct size. Molecular analysis revealed decreased phosphorylation of PI3K/Akt and ERK1/2 pathways associated with reduced expression of PGC-1α and PPARα. Likewise, expression of OXPHOS genes such as atp5O, cycs, cox5b, and ndufb5 was also reduced. Fn14 -/- mice showed significantly improved left ventricular function and PGC-1α levels after MI compared to their respective WT littermates (Fn14 +/+. Finally, inhibition of intrinsic TWEAK with anti-TWEAK antibodies resulted in improved left ventricular function and survival. Conclusions. TWEAK exerted maladaptive effects in mice after myocardial infarction most likely via direct effects on cardiomyocytes. Analysis of the potential mechanisms revealed that TWEAK reduced metabolic adaptations to increased cardiac workload by inhibition of PGC-1α.

  7. Occlusive acute myocardial infarct on 16 multidetector-row helical CT: an experimental study in rabbits

    International Nuclear Information System (INIS)

    Lee, Jeong Kyong; Kim, Yoo Kyung; Lee, Sun Wha; Cho, Min Sun; Choe, Yeon Hyeon

    2006-01-01

    We wanted to evaluate the findings and diagnostic accuracy of MDCT for diagnosing occlusive acute myocardial infarction rabbits. Myocardial infarction was induced in 14 rabbits. MDCT was performed in the early and delay phases at 1 minute and 6 minutes, respectively, after intravenous contrast injection. The rabbits were sacrificed after scanning. The cardiac specimens were sliced and then stained with triphenyltetrazolium chloride (TTC). The agreement in the transmural extent of infarction between the MDCT scans and the TTC-stained specimens were analyzed by using kappa values. Acute myocardial infarction was found in 9 of 14 rabbits on the TTC-stained specimens and MDCT. The infarcted myocardium was demonstrated as a low-attenuation area on the early phase and as a central low-attenuation area with rim-like enhancement along the endocardial and pericardial sides of the myocardial wall on the delay phase. There was excellent agreement in the scores of the transmural extent of myocardial infarction between the TTC-stained specimens and the early phase scan (kappa value = 0.882, ρ 0.000), and there was fair to good agreement between the TTC-stained specimens and the delay phase scan (kappa value = 0.439, ρ = 0.000). Microscopic examination of the cardiac specimens revealed necrosis of myocardial cells in the central portion and granulation tissue along the endocardial and pericardial sides of the necrotic myocardium. 16 slice MDCT scan was useful for the diagnosis of acute myocardial infarction. The early phase scan was more accurate than the delay phase scan for evaluating the transmural extent of myocardial infarction. Histopathologic examination suggested that the low-attenuation area on the delay phase might correspond to necrotic myocardium and the enhanced might correspond to granulation tissue

  8. [Role of catecholamine in activating glycogenolysis in experimental myocardial infarct complicated by ventricular fibrillation].

    Science.gov (United States)

    Dolgova, N P

    1982-01-01

    The experiments on anaesthetized dogs have shown that with artificial ventilation and open chest adrenalin in arrhythmogenic and nonarrythmogenic doses enhances glycogenolysis in the heart proportionally to the dose used Block of beta-adrenergic receptors by propranolol decreased the activation of glycogenolysis in the ischaemic zone and the frequency of ventricular fibrillation after occlusion of the coronary artery. Exhaustion of noradrenaline reserves by reserpin does not influence the intensity of glycogenolysis and the frequency of fibrillation in the acute period of myocardial infarction. It is believed that the activation of glycogenolysis in experimental myocardial infarction is related to the action of adrenalin.

  9. Detection of experimental acute myocardial infarction in dogs with electron beam CT

    International Nuclear Information System (INIS)

    Zhang Minguang; Song Zhijian; Shen Tianzhen; Zuo Huansen; Feng Xiaoyuan; Chen Xingrong

    1999-01-01

    Objective: The value and limitation of discovering the site, shape, density and size of acute myocardial infarction with enhanced volume scans of electron beam computed tomography (EBCT) in experimental dogs were assessed. Methods: The anterior descending and circumflex branches of the left coronary artery were ligated and infarction in the wall of left ventricle was created in six dogs. Enhancement volume scan was made with a EBCT scanner at 1.5, 6, 12, and 20 hour after the ligation and CT sectional images of dog heart were obtained. After finishing the scanning, the dogs were then scarified, and the samples were sent for electron and optic microscopes for pathologic examination. The morphologic findings of myocardial ischemia and infarction in CT images were carefully analysed. The CT numbers and the ratios of left ventricular myocardial and luminal CT number (M/L) in the myocardial ischemic and infarcted areas and normal areas were calculated. Results: The typical myocardial infarction in areas ligated were confirmed by ECG and pathology 20 hours after ligation. The site and shape of acute myocardial infarction were clearly shown on the EBCT images. The density of the ischemia and infarction area was significantly lower than that of the normal myocardium (P < 0.001). M/Ls of the low density areas and normal areas were 13.2% and 32.9%, respectively. The difference was significant (P < 0.001). Conclusions: With adequate scanning technique, the site shape, density and size of acute myocardial ischemia and infarction can be accurately assessed by EBCT

  10. Refractory hyperglycaemia induced by glucose-insulin-potassium infusion in acute myocardial infarction

    NARCIS (Netherlands)

    Svilaas, Tone; van der Horst, I.C.C.; Nijsten, M.W.N.; Zijlstra, F.

    2006-01-01

    Background. Recent randomised clinical trials have not confirmed the beneficial effects of glucose-insulin-potassium (GIK) infusion observed in experimental models of myocardial ischaemia and infarction. Methods. We investigated glucose levels and insulin dose in 107 patients treated with

  11. Liraglutide-induced reduction of myocardial ischemia- reperfusion ...

    African Journals Online (AJOL)

    ischemia/reperfusion injury. Jci Insight 2016; 1(19): e90931. 16. Wang Y, Zhang H, Chai F, Liu X, Berk M. The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression. BMC Psychiatry 2014; 14(1): 349. 17. Liu Z, Chen JM, ...

  12. Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats

    OpenAIRE

    Li, Xiaoqing; Cheng, Qinghong; Li, Jianhua; He, Yonglai; Tian, Peigang; Xu, Chao

    2017-01-01

    Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well ...

  13. Effect of D-003 on isoproterenol-induced myocardial necrosis in rats.

    Science.gov (United States)

    Carbajal, Daisy; Noa, Miriam; Molina, Vivian; Arruzazabala, Maria Lourdes; Más, Rosa; Mendoza, Sarahí; González, Jorge

    2003-01-01

    D-003 is a mixture of high-molecular-weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isoproterenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objective of this study was to determine whether D-003 shows protective effects against ISO-induced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25-400 mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5-200 mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investigated. D-003 administered as single doses dose-dependently decreased necrosis area, percent of infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, but only the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment with ASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs was unchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necrosis indicators in a dose-dependent manner, with results effective from 25 mg/kg to the highest dose tested, indicating that the repeated dose scheme was more effective to prevent the damage. It is concluded that D-003 shows a protective effect on the myocardial necrosis induced by ISO in rats.

  14. [Acute myocardial infarct caused by nicotine-induced erythrocytosis].

    Science.gov (United States)

    Andreas, S; Herrmann, K S; Kreuzer, H; Wiegand, V

    1989-10-02

    A 29-year-old heavy smoker presented with an acute myocardial infarction and hematocrit of 70%. At immediate coronary angiography a complete occlusion of the right coronary artery was found. After intracoronary urokinase the coronary arteries were found to be completely normal. Causes for the erythrocytosis other than smoking could be excluded. We conclude that thrombotic coronary occlusion with acute myocardial infarction was caused by erythrocytosis due to heavy smoking.

  15. The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial ischemia/reperfusion injury in a rat model of diabetes mellitus.

    Science.gov (United States)

    Zhao, Bo; Gao, Wen-Wei; Liu, Ya-Jing; Jiang, Meng; Liu, Lian; Yuan, Quan; Hou, Jia-Bao; Xia, Zhong-Yuan

    2017-10-01

    Myocardial ischemia/reperfusion injury can lead to severe brain injury. Glycogen synthase kinase 3 beta is known to be involved in myo-cardial ischemia/reperfusion injury and diabetes mellitus. However, the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear. In this study, we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats. Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin. Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery. Post-conditioning comprised three cycles of ischemia/reperfusion. Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion, the structure of the brain was seriously damaged in the experimental rats compared with normal controls. Expression of Bax, interleukin-6, interleukin-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, and cleaved caspase-3 in the brain was significantly increased, while expression of Bcl-2, interleukin-10, and phospho-glycogen synthase kinase 3 beta was decreased. Diabetes mellitus can aggravate inflammatory reactions and apoptosis. Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes. Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glyco-gen synthase kinase 3 beta. According to these results, glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.

  16. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease.

    Directory of Open Access Journals (Sweden)

    Elena Nobili

    Full Text Available BACKGROUND: Cysteinyl-leukotrienes (cys-LT are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe(-/- mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2 in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia. METHODS AND PRINCIPAL FINDINGS: Myocardial biopsies from Apoe(-/- mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C(4 synthase (LTC(4S and CysLT1 expression in the myocardium of Apoe(-/- mice. Acute bouts of hypoxia further induced LTC(4S expression, increased LTC(4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe(-/- mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC(4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling. CONCLUSION: Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea.

  17. Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Torii, Yukio (Kyoto Prefectural Univ. of Medicine (Japan))

    1983-09-01

    I studied experimentally the myocardial uptake of /sup 201/Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that /sup 201/Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia.

  18. Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats.

    Directory of Open Access Journals (Sweden)

    Hua Li

    Full Text Available BACKGROUND: Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms. METHODOLOGY: Paeonol (80 mg kg(-1 and danshensu (160 mg kg(-1 were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg(-1 subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg(-1 to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed. PRINCIPAL FINDINGS: Induction of rats with isoproterenol resulted in a marked (P<0.001 elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001 decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating

  19. Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

    NARCIS (Netherlands)

    Smeding, Lonneke; Kuiper, Jan Willem; Plotz, Frans B.; Kneyber, Martin C. J.; Groeneveld, A. B. Johan

    2013-01-01

    Background: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex

  20. Cardioprotective Effects of HuoxueAnshen Recipe against Myocardial Injuries Induced by Sleep Deprivation in Rats

    Directory of Open Access Journals (Sweden)

    Rong Yuan

    2017-01-01

    Full Text Available Background. Traditional Chinese Medicine is extensively used in China and HuoxueAnshen Recipe (HAR was formulated according to its method in treating CHD accompanied with insomnia in clinic. However, there are few studies related to the effect of HAR on myocardial injury and sleep disorders. Purpose. To investigate the effects of HAR on sleep deprivation- (SD- induced myocardial I/R injury. Methods. Male Wistar rats receiving a daily gavage of HAR or vehicle were exposed to SD intervention while control rats had normal sleep. Then all rats were exposed to myocardial I/R. Hormone, vascular endothelial, and inflammatory related factors were detected before and after I/R, while cardiac injury, cardiac function, myocardial infarct size, and apoptosis were detected after I/R. Results. Levels of neuropeptide Y, vascular endothelial and inflammatory related factors were significantly increased while melatonin was decreased in vehicle-treated SD rats but not in HAR-treated SD rats after SD. In addition, cardiac injury, cardiac dysfunction, myocardial infarct size, and myocardial apoptosis were deteriorated in vehicle-treated SD rats but were ameliorated in HAR-treated SD rats after I/R. Conclusion. HAR not only improved SD-induced hormone disorders, inflammation, and endothelial dysfunction, but also alleviated I/R injury, which supports protective usage in CHD and psychocardiology.

  1. Magnesium supplementation prevents angiotensin II-induced myocardial damage and CTGF overexpression.

    Science.gov (United States)

    Finckenberg, Piet; Merasto, Saara; Louhelainen, Marjut; Lindgren, Leena; Vapaatalo, Heikki; Müller, Dominik N; Luft, Friedrich C; Mervaala, Eero M A

    2005-02-01

    Magnesium deficiency promotes vasoconstriction and myocardial damage. Recent studies provide evidence that Ang II mobilizes intracellular Mg through AT1 receptor-mediated pathways. We tested the hypothesis of whether magnesium supplementation prevents Ang II-induced myocardial damage and induction of the profibrotic connective tissue growth factor (CTGF). Four-week-old double transgenic rats harboring human renin and angiotensinogen genes (dTGR) were given dietary magnesium supplementation (0.6%) for 3 weeks. Control dTGR and normotensive Sprague-Dawley (SD) rats received normal diet (Mg 0.2%). Histopathological, immunohistochemical and mRNA analysis were used to detect the treatment-related effects of dietary magnesium in dTGR. Magnesium (Mg) supplementation decreased blood pressure, ameliorated cardiac hypertrophy, protected against the development of Ang II-induced myocardial damage and increased serum ionized Mg2+ concentration (all variables P protein expressions were increased by 300% in dTGR (P supplementation prevented Ang II-induced myocardial CTGF overexpression (P supplementation also improved the therapeutic effects of the calcineurin inhibitor tacrolimus, which produced marked hypomagnesemia when given as monotherapy. Our findings suggest a salutary effect for magnesium supplementation in the treatment of Ang II-induced myocardial complications.

  2. High concordance between mental stress-induced and adenosine-induced myocardial ischemia assessed using SPECT in heart failure patients : Hemodynamic and biomarker correlates

    NARCIS (Netherlands)

    Wawrzyniak, A.J.; Dilsizian, V.; Krantz, D.S.; Harris, K.M.; Smith, M.F.; Shankovich, A.; Whittaker, K.S.; Rodriguez, G.A.; Gottdiener, J.S.; Li, J.; Kop, W.J.; Gottlieb, S.S.

    2015-01-01

    Mental stress can trigger myocardial ischemia, but the prevalence of mental stress–induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress–induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with

  3. Hyperkalemia induced pseudo-myocardial infarction in septic shock

    Directory of Open Access Journals (Sweden)

    S E Pothiawala

    2014-01-01

    Full Text Available Hyperkalemia is an acute life-threatening disorder presenting to the emergency department. Patients with hyperkalemia may manifest characteristic electrocardiographic changes including tented T waves, widening of the QRS complex and loss of P waves, sine wave pattern and eventually asystole. There have been only few reports of hyperkalemia causing ST segment elevation on electrocardiogram simulating an acute myocardial infarction. This case describes pseudo-myocardial infarction due to hyperkalemia and septic shock. Rapid determination of serum potassium levels by bedside blood gas analyzers serves to be a useful guide. ST segment elevation related to hyperkalemia will resolve with successful reduction of the serum potassium levels by appropriate therapy. It is important for physicians to be aware of this condition as this will aid in initiating correct therapy and prevent the patient from unnecessary interventions and the associated risk of complications.

  4. Phenelzine-induced myocardial injury: a case report.

    Science.gov (United States)

    Ngo, Adeline Su-Yin; Ho, Raymond Y; Olson, Kent R

    2010-12-01

    Phenelzine is an irreversible monoamine oxidase inhibitor (MAOI). Hypertensive reactions after ingestion of tyramine-rich foods such as cheese are well known. However, a review of the available medical literature found no previous reports of myocardial infarction resulting from the ingestion of cheese by a patient taking a MAOI. A 34-year-old female taking phenelzine for depression developed severe chest pain 1 h after eating cheese. She was hypertensive and the electrocardiography showed ischemic changes in the antero-lateral chest leads. The chest pain and elevated blood pressure were relieved with intravenous morphine and nitroprusside. The initial serum troponin I level was normal, but serial repeat levels showed a rising trend with a peak at 4.89 ug/L (reference range home after a hospital stay of 3 days. We believe this to be the first reported case of myocardial infarction resulting from ingestion of cheese in a patient taking a MAOI. It might be expected that hypertensive crisis could lead to a myocardial infarction, but a review of the medical literature found no such cases reported.

  5. Early upregulation of myocardial CXCR4 expression is critical for dimethyloxalylglycine-induced cardiac improvement in acute myocardial infarction.

    Science.gov (United States)

    Mayorga, Mari; Kiedrowski, Matthew; Shamhart, Patricia; Forudi, Farhad; Weber, Kristal; Chilian, William M; Penn, Marc S; Dong, Feng

    2016-01-01

    The stromal cell-derived factor-1 (SDF-1):CXCR4 is important in myocardial repair. In this study we tested the hypothesis that early upregulation of cardiomyocyte CXCR4 (CM-CXCR4) at a time of high myocardial SDF-1 expression could be a strategy to engage the SDF-1:CXCR4 axis and improve cardiac repair. The effects of the hypoxia inducible factor (HIF) hydroxylase inhibitor dimethyloxalylglycine (DMOG) on CXCR4 expression was tested on H9c2 cells. In mice a myocardial infarction (MI) was produced in CM-CXCR4 null and wild-type controls. Mice were randomized to receive injection of DMOG (DMOG group) or saline (Saline group) into the border zone after MI. Protein and mRNA expression of CM-CXCR4 were quantified. Echocardiography was used to assess cardiac function. During hypoxia, DMOG treatment increased CXCR4 expression of H9c2 cells by 29 and 42% at 15 and 24 h, respectively. In vivo DMOG treatment increased CM-CXCR4 expression at 15 h post-MI in control mice but not in CM-CXCR4 null mice. DMOG resulted in increased ejection fraction in control mice but not in CM-CXCR4 null mice 21 days after MI. Consistent with greater cardiomyocyte survival with DMOG treatment, we observed a significant increase in cardiac myosin-positive area within the infarct zone after DMOG treatment in control mice, but no increase in CM-CXCR4 null mice. Inhibition of cardiomyocyte death in MI through the stabilization of HIF-1α requires downstream CM-CXCR4 expression. These data suggest that engagement of the SDF-1:CXCR4 axis through the early upregulation of CM-CXCR4 is a strategy for improving cardiac repair after MI. Copyright © 2016 the American Physiological Society.

  6. Correlation between oxidative stress and alteration of intracellular calcium handling in isoproterenol-induced myocardial infarction.

    Science.gov (United States)

    Díaz-Muñoz, Mauricio; Alvarez-Pérez, Marco Antonio; Yáñez, Lucía; Vidrio, Susana; Martínez, Lidia; Rosas, Gisele; Yáñez, Mario; Ramírez, Sotero; de Sánchez, Victoria Chagoya

    2006-09-01

    Myocardial Ca(2+) overload and oxidative stress are well documented effects associated to isoproterenol (ISO)-induced myocardial necrosis, but information correlating these two issues is scarce. Using an ISO-induced myocardial infarction model, 3 stages of myocardial damage were defined: pre-infarction (0-12 h), infarction (12-24 h) and post-infarction (24-96 h). Alterations in Ca(2+) homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca(2+) content, the activity of Ca(2+) handling proteins, and by quantifying TBARs, nitric oxide (NO) and oxidative protein damage (changes in carbonyl and thiol groups). Free radicals generated system, antioxidant enzymes and oxidative stress (GSH/GSSG ratio) were also monitored at different times of ISO-induced cardiotoxicity. The Ca(2+) overload induced by ISO was counterbalanced by a diminution in the ryanodine receptor activity and the Na(+)-Ca(+2) exchanger as well as by the increase in both calcium ATPases activities (vanadate- and thapsigargine-sensitive) and mitochondrial Ca(2+) uptake during pre-infarction and infarction stages. Pro-oxidative reactions and antioxidant defences during the 3 stages of cardiotoxicity were observed, with maximal oxidative stress during the infarction. Significant correlations were found among pro-oxidative reactions with plasmalemma and sarcoplasmic reticulum Ca(2+) ATPases, and ryanodine receptor activities at the onset and development of ISO-induced infarction. These findings could be helpful in the design of antioxidant therapies in this pathology.

  7. NF-κB involvement in hyperoxia-induced myocardial damage in newborn rat hearts.

    Science.gov (United States)

    Zara, Susi; De Colli, Marianna; Rapino, Monica; Di Valerio, Valentina; Marconi, Guya Diletta; Cataldi, Amelia; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea

    2013-11-01

    Premature newborns are frequently exposed to hyperoxia ventilation and some literature data indicate the possibility of hyperoxia-induced myocardial damage. Since nuclear factor κB (NF-κB) is a crucial signaling molecule involved in physiological response to hyperoxia in different cell types as well as in various tissues, our attention has been focused on the role played by NF-κB pathway in response to moderate and severe hyperoxia exposure in rat neonatal heart tissue. Akt and IκBα levels, involved in NF-κB activation, along with the balance between apoptotic and survival pathways have also been investigated. Experimental design of the study has involved exposure of newborn rats to room air (controls), 60 % O2 (moderate hyperoxia), or 95 % O2 (severe hyperoxia) for the first two postnatal weeks. Morphological analysis shows a less compact tissue in rat heart exposed to moderate hyperoxia and a decreased number of nuclei in samples exposed to severe hyperoxia. A significant increase of NF-κB positive nuclei percentage and p-IκBα expression in samples exposed to 95 % hyperoxia compared to control and to 60 % hyperoxia is evidenced; in parallel, an increase of pAkt/Akt ratio in both samples exposed to 95 and 60 % hyperoxia is shown. Furthermore, a more evident cytochrome c/Apaf-1 immunocomplex and a decreased Bcl2 expression in 95 % hyperoxia-exposed sample compared to 60 % exposed one is evidenced. In conclusion, our findings suggest the involvement of the NF-κB pathway and Akt signaling in the mechanisms of myocardial hyperoxic damage in the newborns, with particular reference to the induction of oxidative stress-related apoptosis.

  8. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian [Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shahzamani, Mehran [Department of Cardiovascular Surgery, Isfahan University of Medical Sciences, Tehran (Iran, Islamic Republic of); Takhtfooladi, Mohammad Ashrafzadeh, E-mail: dr-ashrafzadeh@yahoo.com [Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Allahverdi, Amin [Department of Surgery, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khansari, Mohammadreza [Department of Physiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2015-08-15

    Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  9. Titanium dioxide nanoparticle-induced cytotoxicity and the underlying mechanism in mouse myocardial cells

    Science.gov (United States)

    Zhou, Yingjun; Hong, Fashui; Wang, Ling

    2017-11-01

    Exposure to fine particulate matter (PM) is known to cause cardiovascular disease. While extensive research has focused on the risk of atmospheric PM to public health, particularly heart disease, limited studies to date have attempted to clarify the molecular mechanisms underlying myocardial cell damage caused by exposure to titanium dioxide nanoparticles (TiO2 NPs). Data from the current investigation showed that TiO2 NPs are deposited in myocardial mitochondria via the blood circulation accompanied by obvious ultrastructural changes and impairment of mitochondrial structure and function in mouse myocardial cells, including reduction in mitochondrial membrane potential and ATP production, aggravation of oxidative stress along with increased levels of reactive oxygen species, malondialdehyde and protein carbonyl, and decreased glutathione content and enzymatic activities, including superoxide dismutase and glutathione peroxidase. Furthermore, TiO2 NPs induced a significant decrease in the activities of complex I, complex II, complex III, complex IV, succinate dehydrogenase, NADH oxidase, Ca2+-ATPase, Na+/K+-ATPase, and Ca2+/Mg2+-ATPase, and upregulation of cytokine expression (including cytochrome c, caspase-3, and p-JNK) in mitochondria-mediated apoptosis while downregulating Bcl-2 expression in mouse myocardial cells. Our results collectively indicate that chronic exposure to TiO2 NPs induces damage in mitochondrial structure and function as well as mitochondria-mediated apoptosis in mouse myocardial cells, which may be closely associated with heart disease in animals and humans.

  10. Myocardial perfusion imaging, coronary angiography and histological examination in experimental treatment of Ad-HGF for myocardial infarction

    International Nuclear Information System (INIS)

    Li Jianhua; Feng Jianlin; Cheng Xu; Li Dianfu; Zhang Youfu

    2007-01-01

    Objective: Gene therapy has drawn a great attention. A swine model of adenovirus hepatocyte growth factor(Ad-HGF) treated myocardial infarction(MI) was utilized, with the effect being assessed by rest myocardial perfusion imaging, coronary angiography and histological examination. Methods: Three groups of MI swine treated with Ad-HGF at low dose [n=5, Ad-HGF 10 8 plague forming unit (PFU)/ site], medium dose(n=5, 4 x 10 8 PFU/site), and high dose (n=5, 5 x 10 9 PFU/site), a control group treated with normal saline(NS, n=5) and a blank control group (n=5) underwent rest myocardial perfusion imaging and coronary angiography before and after treatment. The imaging results were analyzed along with histological findings in each group. Results: The state of myocardial perfusion and Rentrop scores remained unchanged in the blank control and NS groups after treatment. Whereas there was a significant improvement in the two variables in all three groups treated with Ad-HGF. The scores of left circumflex coronary artery (LCX) before and after treated were 7.8 ± 1.3 and 16.4 ± 1.1 (low-dose), 8.2 ± 1.6 and 17.6 ± 0.9 (medium-dose), 8.4 ± 1.5 and 19.0 ± 0.7 (high-dose), respectively. No significant differences were noted among the 3 groups. The number of vessels of NS group was markedly less than that of other groups. Conclusion: Myocardial perfusion imaging seems to be more accurate than coronary angiography and histological examination in evaluating the effects of Ad-HGF on myocardial infarction. (authors)

  11. Myocardial mechanical dysfunction and calcium overload following rewarming from experimental hypothermia in vivo.

    Science.gov (United States)

    Kondratiev, Timofei V; Wold, Ragnhild M; Aasum, Ellen; Tveita, Torkjel

    2008-02-01

    Rewarming patients from accidental hypothermia are regularly complicated with cardiovascular instability ranging from minor depression of cardiac output to fatal circulatory collapse also termed "rewarming shock". Since altered Ca2+ handling may play a role in hypothermia-induced heart failure, we studied changes in Ca2+ homeostasis in in situ hearts following hypothermia and rewarming. A rat model designed for studies of the intact heart in a non-arrested state during hypothermia and rewarming was used. Rats were core cooled to 15 degrees C, maintained at 15 degrees C for 4h and thereafter rewarmed. As time-matched controls, one group of animals was kept at 37 degrees C for 5h. Total intracellular myocardial Ca2+ content ([Ca2+]i) was measured using 45Ca2+. Following rewarming we found a significant reduction of stroke volume and cardiac output compared to prehypothermic control values as well as to time-matched controls. Likewise, we found that hypothermia and rewarming resulted in a more than six-fold increase in [Ca2+]i to 3.01+/-0.43 micromol/g dry weight compared to 0.44+/-0.05 micromol/g dry weight in normothemia control. These findings indicate that hypothermia-induced alterations in the Ca2+-handling result in Ca2+ overload during hypothermia, which may contribute to myocardial failure during and after rewarming.

  12. Dietary fenugreek (Trigonella foenum-graecum seeds and garlic (Allium sativum alleviates oxidative stress in experimental myocardial infarction

    Directory of Open Access Journals (Sweden)

    P. Mukthamba

    2017-06-01

    Full Text Available Soluble fiber-rich fenugreek seeds (Trigonella foenum-graecum and garlic (Allium sativum are understood to exert cholesterol-lowering and antioxidant effects. The cardioprotective influence of a combination of fenugreek seeds and garlic by their antioxidant influence was evaluated in hypercholesterolemic rats administered isoproterenol. Wistar rats were maintained on high-cholesterol diet for 8 weeks along with dietary interventions of fenugreek (10%, garlic (2% and their combination. Myocardial infarction was induced with isoproterenol injection. Increased circulatory troponin, disturbed activities of cardiac ATPases, increased serum iron and decreased ceruloplasmin confirmed myocardial infarction. Elevated lipid peroxides accompanied with reduced antioxidant molecules caused by isoproterenol and altered activities of antioxidant enzymes in serum and heart in induced myocardial necrosis were countered by dietary fenugreek, garlic, and fenugreek + garlic. Dietary fenugreek seeds and garlic ameliorated isoproterenol-induced compromised antioxidant status, the cardioprotective effect being higher by the combination of fenugreek seeds and garlic.

  13. Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms.

    Science.gov (United States)

    Vaccarino, Viola; Sullivan, Samaah; Hammadah, Muhammad; Wilmot, Kobina; Al Mheid, Ibhar; Ramadan, Ronnie; Elon, Lisa; Pimple, Pratik M; Garcia, Ernest V; Nye, Jonathon; Shah, Amit J; Alkhoder, Ayman; Levantsevych, Oleksiy; Gay, Hawkins; Obideen, Malik; Huang, Minxuan; Lewis, Tené T; Bremner, J Douglas; Quyyumi, Arshed A; Raggi, Paolo

    2018-02-20

    Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown. We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received 99m Tc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress. The mean age of the sample was 50 years (range, 22-61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%, P =0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%, P =0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in

  14. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  15. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Hasan Ali Kiraz

    2015-12-01

    Full Text Available Objective: Ischemia/reperfusion (I/R injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg were randomly divided into three equal groups as follows: the diabetic I/R group (DIR in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL, which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC which underwent sham operations without tightening of the coronary sutures. As a control group (C, six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p=0.008. Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively. Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001. Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively. Also, myocardial tissue edema was significantly different among groups (p=0.006. The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively. Conclusion: Taken together, our data

  16. Exercise-induced thallium-201 myocardial perfusion defects in angina pectoris without significant coronary artery stenosis

    International Nuclear Information System (INIS)

    Nakazato, Masayasu; Maruoka, Yuji; Sunagawa, Osahiko; Kinjo, Kunihiko; Tomori, Masayuki; Fukiyama, Koshiro

    1990-01-01

    We performed exercise thallium-201 myocardial scintigraphy in 32 patients with angina pectoris to study the incidence of perfusion defects, who had no significant organic stenosis on coronary angiography. None of them had myocardial infarction or cardiomyopathy. Thallium-201 myocardial scintigraphy and 12-lead ECG recording were performed during supine bicycle ergometer exercise. Perfusion defects in thallium-201 scintigrams in SPECT images were assessed during visual analysis by two observers. In the coronary angiograms obtained during intravenous infusion of nitroglycerin, the luminal diameter of 75% stenosis or less in the AHA classification was regarded as an insignificant organic stenosis. Myocardial perfusion defects in the thallium-201 scintigrams were detected in eight (25%) of the 32 patients. Six of these eight patients had variant angina documented during spontaneous attacks with ST elevations in standard 12-lead ECGs. Perfusion defects were demonstrated at the inferior or infero-posterior regions in six patients, one of whom had concomitant anteroseptal defect. The defects were not always accompanied by chest pain. All but one patient demonstrating inferior or inferoposterior defects showed ST depression in leads II, III and aV F on their ECGs, corresponding to inferior wall ischemia. The exception was a case with right bundle branch block. Thus, 25% of the patients with angina pectoris, who had no evidence of significant organic stenosis on their coronary angiograms, exhibited exercise-induced perfusion defects in their thallium-201 scintigrams. Coronary spasms might have caused myocardial ischemia in these patients. (author)

  17. Exercise-induced thallium-201 myocardial perfusion defects in angina pectoris without significant coronary artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Nakazato, Masayasu; Maruoka, Yuji; Sunagawa, Osahiko; Kinjo, Kunihiko; Tomori, Masayuki; Fukiyama, Koshiro (Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine)

    1990-01-01

    We performed exercise thallium-201 myocardial scintigraphy in 32 patients with angina pectoris to study the incidence of perfusion defects, who had no significant organic stenosis on coronary angiography. None of them had myocardial infarction or cardiomyopathy. Thallium-201 myocardial scintigraphy and 12-lead ECG recording were performed during supine bicycle ergometer exercise. Perfusion defects in thallium-201 scintigrams in SPECT images were assessed during visual analysis by two observers. In the coronary angiograms obtained during intravenous infusion of nitroglycerin, the luminal diameter of 75% stenosis or less in the AHA classification was regarded as an insignificant organic stenosis. Myocardial perfusion defects in the thallium-201 scintigrams were detected in eight (25%) of the 32 patients. Six of these eight patients had variant angina documented during spontaneous attacks with ST elevations in standard 12-lead ECGs. Perfusion defects were demonstrated at the inferior or infero-posterior regions in six patients, one of whom had concomitant anteroseptal defect. The defects were not always accompanied by chest pain. All but one patient demonstrating inferior or inferoposterior defects showed ST depression in leads II, III and aV{sub F} on their ECGs, corresponding to inferior wall ischemia. The exception was a case with right bundle branch block. Thus, 25% of the patients with angina pectoris, who had no evidence of significant organic stenosis on their coronary angiograms, exhibited exercise-induced perfusion defects in their thallium-201 scintigrams. Coronary spasms might have caused myocardial ischemia in these patients. (author).

  18. Cardioprotective effect of total saponins from three medicinal species of Dioscorea against isoprenaline-induced myocardial ischemia.

    Science.gov (United States)

    Tang, Yi-Na; He, Xi-Cheng; Ye, Min; Huang, Hao; Chen, Hong-Li; Peng, Wan-Ling; Zhao, Zhong-Zhen; Yi, Tao; Chen, Hu-Biao

    2015-12-04

    As folk medicines used in China since 1950s, Dioscorea nipponica Makino (DN), D. panthaica Prain et Burkill (DP), and D. zingiberensis C.H. Wright (DZ) are regarded as having more or less the same traditional therapeutic actions, such as activating blood, relieving pain, and dispersing swelling. It is noteworthy that, of the 49 species of the genus Dioscorea distributed in China, based on such traditional efficacies, only these three have been further developed as effective single-herb medicines for treating cardiovascular diseases by the modern pharmaceutical industry. In our previous study, it was found that the chemical compositions of DN and DP were similar, and both were distinct from that of DZ. Hence, whether their different chemical profiles support their anti-IHD (ischemic heart disease) activity in common still needs to be answered. So far it is still unknown whether the efficacies of these three herbs act via similar mechanism and whether they possess comparable therapeutic efficacy for experimental myocardial ischemia (MI). The present study aimed to further investigate the underlying mechanisms with respect to antioxidative stress activity by which these Dioscorea spp. attenuate MI, and to compare the therapeutic effect of total saponins from these three species on myocardial antioxidant levels and myocardial histology. The serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), total superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), the total antioxidant capacity (T-AOC), and malondialdehyde (MDA), as well as myocardial histology, were compared among rat groups administered with total saponins (TS) of DN, DP or DZ (abbreviated as DNTS, DPTS and DZTS, respectively). The rats experienced myocardial ischemia induced by isoprenaline (ISO) injection; the test solutions (DNTS, DPTS, DZTS) were administered either after the ISO injection, or both before and after. Compared with the model

  19. Quantitative and morphological analysis of the computed tomographic images in experimental myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, Yasuaki

    1984-12-01

    Experimental myocardial infarction in the dog was evaluated by the cardiac scan system developed together by the Department of Radiology, Dokkyo University Hospital, and Toshiba Co. Ltd. Analysis of the CT image of myocardial infarction treated by ligating the coronary arteries demonstrated the following: 1) In perfusion phase representing initial 4 min after injection of the contrast material, infarcted areas were shown as areas of low density. Pattern of these low dense areas appeared homogeneous and correlated quite well with the infarcted areas proved on necropsy. 2) In delayed scan performed between 8-12 min after the infusion of the contrast material, delayed enhancement occurred, for which visual pattern was quite variable from case to case. 3) In gated scan, time-related to ECG cycle, pictures of end-diastole (ED) and end-systole (ES) in cardiac cycle were aquired. And alteration rates of endocardial space, (ED-ES/ED) x 100%, were obtained by dividing CT sliced endocardial space into 16 segments. By using these rates, abnormal motion of the infarcted area and compensatory motion of the normal myocardium were analyzed quantitatively. (author).

  20. Danqi Pill regulates lipid metabolism disorder induced by myocardial ischemia through FATP-CPTI pathway.

    Science.gov (United States)

    Wang, Yong; Li, Chun; Wang, Qiyan; Shi, Tianjiao; Wang, Jing; Chen, Hui; Wu, Yan; Han, Jing; Guo, Shuzhen; Wang, Yuanyuan; Wang, Wei

    2015-02-21

    Danqi Pill (DQP), which contains Chinese herbs Salvia miltiorrhiza Bunge and Panax notoginseng, is widely used in the treatment of myocardial ischemia (MI) in China. Its regulatory effects on MI-associated lipid metabolism disorders haven't been comprehensively studied so far. We aimed to systematically investigate the regulatory mechanism of DQP on myocardial ischemia-induced lipid metabolism disorders. Myocardial ischemia rat model was induced by left anterior descending coronary artery ligation. The rat models were divided into three groups: model group with administration of normal saline, study group with administration of DanQi aqueous solution (1.5 mg/kg) and positive-control group with administration of pravastatin aqueous solution (1.2 mg/kg). In addition, another sham-operated group was set as negative control. At 28 days after treatment, cardiac function and degree of lipid metabolism disorders in rats of different groups were measured. Plasma lipid disorders were induced by myocardial ischemia, with manifestation of up-regulation of triglyceride (TG), low density lipoprotein (LDL), Apolipoprotein B (Apo-B) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR). DQP could down-regulate the levels of TG, LDL, Apo-B and HMGCR. The Lipid transport pathway, fatty acids transport protein (FATP) and Carnitine palmitoyltransferase I (CPTI) were down-regulated in model group. DQP could improve plasma lipid metabolism by up-regulating this lipid transport pathway. The transcription factors peroxisome proliferator-activated receptor α (PPARα) and retinoid X receptors (RXRs), which regulate lipid metabolism, were also up-regulated by DQP. Furthermore, DQP was able to improve heart function and up-regulate ejection fraction (EF) by increasing the cardiac diastolic volume. Our study reveals that DQP would be an ideal alternative drug for the treatment of dyslipidemia which is induced by myocardial ischemia.

  1. Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Chen-Hui Ju

    2015-07-01

    Full Text Available Background/Aims: After myocardial infarction (MI, cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate-conductance calcium-activated potassium Channel (KCa3.1 has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms. Methods: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs stimulated by angiotensin II (Ang II was tested. Results: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways. Conclusion: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro-fibrotic effects of CFs.

  2. Impaired resting myocardial annular velocities are independently associated with mental stress-induced ischemia in coronary heart disease.

    Science.gov (United States)

    Ersbøll, Mads; Al Enezi, Fawaz; Samad, Zainab; Sedberry, Brenda; Boyle, Stephen H; O'Connor, Christopher; Jiang, Wei; Velazquez, Eric J

    2014-04-01

    The aim of this study was to investigate the association between resting myocardial function as assessed by tissue Doppler myocardial velocities and the propensity to develop mental stress-induced ischemia (MSIMI). Tissue Doppler myocardial velocities detect preclinical cardiac dysfunction and clinical outcomes in a range of conditions. However, little is known about the interrelationship between myocardial velocities and the propensity to develop MSIMI compared with exercise stress-induced myocardial ischemia. Resting annular myocardial tissue Doppler velocities were obtained in 225 patients with known coronary heart disease who were subjected to both conventional exercise stress testing as well as a battery of 3 mental stress tests. Diastolic early (e') and late (a') as well as systolic (s') velocities were obtained, and the eas index, an integrated measure of myocardial velocities, was calculated as e'/(a' × s'). MSIMI was defined as: 1) the development or worsening of regional wall motion abnormality; 2) a reduction in left ventricular ejection fraction ≥ 8%; and/or 3) ischemic ST-segment changes during 1 or more of the 3 mental stress tests. A total of 98 of 225 patients (43.7%) exhibited MSIMI. Patients developing MSIMI had significantly lower s' (7.0 ± 1.7 vs. 7.5 ± 1.2, p = 0.016) and a' (8.9 ± 1.8 vs. 10.0 ± 1.9, p stress-induced myocardial ischemia. MSIMI but not exercise stress-induced myocardial ischemia is independently associated with resting abnormalities in myocardial systolic and late diastolic velocities as well as the integrated measure of the eas index in patients with known coronary artery disease. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Reduction of experimental myocardial infarct size by combined treatment with methylprednisolone sodium succinate and betahistine hydrochloride.

    Science.gov (United States)

    Joyce, L D; Smith, J M; Mauer, H G; Lillehei, R C

    1978-01-01

    This laboratory and others have shown that methylprednisolone sodium succinate and betahistine hydrochloride can each reduce the size of experimental myocardial infarct in dogs at six hours. In light of the fact that these two agents probably act via different mechanisms, a study was carried out to determine if there would be cumulative effects of using these two agents together. Using a left anterior descending coronary artery ligation model to create an experimental myocardial infarction and an intracellular lactic dehydrogenase (LDH) stain to measure the infarct size, 66 dogs were studied. Nineteen dogs served as controls with no therapy; 20 received a continuous intravenous infusion of betahistine hydrochloride (0.24 mg/kg/min) for six hours following ligation; 10 dogs received methylprednisolone sodium succinate intravenously 30 mg/kg at one hour postligation; and 17 other dogs received betahistine hydrochloride intravenously (0.24 mg/kg/min) over six hours following ligation, plus methylprednisolone sodium succinate intravenously (30 mg/kg) at one hour postligation. At six hours, the combined treatment demonstrated no significant improvement over betahistine HCl alone (control, 16.0%; betahistine HCl, 11.4%; combined, 11.2% P less than 0.05). At 24 hours, only the combined treatment group demonstrated a significant infarct size reduction (control, 15.5%; methylprednisolone, 13.1%; betahistine--HCl, 14.2%; combined, 9.7%; P less than 0.0025). Other parameters that were evaluated and analyzed include mean aortic pressure, left atrial pressure, cardiac index, total peripheral resistance, arterial and coronary sinus pH, pCO2, pO2, hematocrit, O2 consumption, O2 content difference, and coronary sinus lactate and creatine phosphokinase (CPK). These results suggest a significant cumulative effect in reducing infarct size over that achieved with one agent alone; however, further studies are needed to determine the appropriate dosage and temporal factors.

  4. [Effect of selenium on the protection of myocardial cells from injuries induced by overloaded reactive oxygen species, and on the expression of actin in myocardial cells].

    Science.gov (United States)

    Tang, Jing; Tan, Wuhong; Zhu, Yanhe; Wang, Lixin; Zhai, Lianbang

    2012-01-01

    To investigate the effect of selenium on the protection of myocardial cells from injuries induced by H2O2 and on the expression of alpha-actin and beta-actin in myocardial cells. Myocardial cells of suckling mice in the culture were divided into six groups: Controls group (without H2O2 or Se), H2O2 group, Se 0.05 micromol/ L group, Se 0.5 micromol/L group, Se 1.0 micromol/L group and Se 5.0 micromol/L group. The ultrastructure of myocardial cells was observed by transmission electron microscope (TEM), and the LDH and MDA contents in the culture media were determined by colorimetry. The expression of alpha-actin and beta-actin in myocardial cells was detected by Western blot. The injury of myocardial cells observed under TEM was attenuated in the 0.5 micromol/L Se group. The LDH and MDA contents in the culture media of the Se groups was higher than the control group (P contents in the 0.5 micromol/L Se group were the lowest in all Se groups. The expression level of alpha-actin and beta-actin in the 0.5 micromol/L Se group is higher than that in the H2O2 group, even higher than the control group. The protective effect of Se on myocardial cells damaged by H2O2 was better in the 0.5 micromol/ LSe group, which could maintain the expression of alpha-actin and beta-actin, even induce the remolding of cytoskeleton proteins.

  5. Experimental radiation-induced leukemia

    International Nuclear Information System (INIS)

    Upton, A.C.

    1977-01-01

    Of the various neoplasms induced by ionizing radiation in human and animal populations, leukemias and lymphomas were among the first to receive systematic study and have remained under intensive investigation up to the present time. The reticular tissue neoplasm that has been the most thoroughly studied is a lymphoma of the thymus which characteristically predominates in whole- bodyirradiated mice. Thanks to intensive research on this tumor, much is now known about its pathogenesis. The purpose of this report is to review the knowledge of pathogenesis of other types of radiation-induced leukemias and lymphomas, in an effort to assess the extent to which the comparative data for all such diseases can be integrated into a single unifying framework

  6. Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    1998-03-01

    Reversible thallium-201 ({sup 201}Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise {sup 201}Tl and rest {sup 123}I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise {sup 201}Tl in 19/28 patients with HCM. {sup 123}I-BMIPP uptake was decreased compared with delayed {sup 201}Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between {sup 123}I-BMIPP and {sup 201}Tl was observed more often in the 49/75 (65%) segments with reversible exercise {sup 201}Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of {sup 123}I-BMIPP and {sup 201}Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

  7. Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study.

    Science.gov (United States)

    Jiang, Wei; Boyle, Stephen H; Ortel, Thomas L; Samad, Zainab; Velazquez, Eric J; Harrison, Robert W; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B; O'Connor, Christopher M; Becker, Richard C

    2015-04-01

    Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation , 43.33% (n=117) met criteria for MSIMI and 18.15% (n=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10μM (6.95[5.54] vs. -14.23[8.75].; P=0.045), epinephrine 10μM (12.84[4.84] vs. -6.40[7.61].; P=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. -27.34[8.34]; Pstress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy ...

    African Journals Online (AJOL)

    Purpose: This study was carried out to investigate the role of hypoxia-inducible factor (HIF) in diabetic cardiomyopathy in vitro. Methods: Hypoxia was induced chemically in H9C2 cells (cardiac hypertrophy model), and the cells were treated with phenylephrine (PE), deferoxamine (DFO), PE + DFO, and HIF-1α siRNA under ...

  9. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

    African Journals Online (AJOL)

    Purpose: This study was carried out to investigate the role of hypoxia-inducible factor (HIF) in diabetic cardiomyopathy in vitro. Methods: Hypoxia was induced chemically in H9C2 cells (cardiac hypertrophy model), and the cells were treated with phenylephrine (PE), deferoxamine (DFO), PE + DFO, and HIF-1α siRNA under.

  10. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    International Nuclear Information System (INIS)

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-01-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls. All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p < 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p < 0.05) and pericardial effusion (p < 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p < 0.05) or IB (p < 0.01) and in the untreated, unirradiated rabbits (p < 0.01). Early administrative of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusin, and improved survival in this experimental model of radiation-induced heart disease

  11. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    International Nuclear Information System (INIS)

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-01-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease

  12. Therapeutic effects of Qishen Yiqi Dropping Pill on myocardial injury induced by chronic hypoxia in rats.

    Science.gov (United States)

    Yu, Fu-Chao; Xu, Yan-Juan; Tong, Jia-Yi; Lu, Zhou-Zhou; Zhang, Xiao-Hui

    2015-10-01

    The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley (SD) rats were randomly divided into three groups: the control, model, and treatment groups (n = 10 per group). The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill (35 mg·kg(-1)·d(-1)) for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor 1α (HIF-1α) were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1α expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular diseases. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  13. Cardioprotective effect of Spathodea campanulata bark on isoproterenol-induced myocardial infarction in rats

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    Abubaker Siddiq

    2012-05-01

    Full Text Available Objective: To evaluate the cardioprotective potential of 70% ethanolic extract of bark of Spathodea campanulata P. Beauv (EEBSC. Methods: Wister strain rats were pretreated with EEBSC in two different doses (250 and 500mg/kg orally for 14 d and then intoxicated with isoproterenol (200 mg/ kg, s.c. for 2 consecutive days at an interval of 24 h on 14th and 15th day of treatment protocol to induce myocardial injury. Results: Cardioprotection was assessed by estimating serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine phosphokinase, triglycerides, total cholesterol, low density lipoproteins and high density lipoproteins. The levels of thiobarbituric acid reactive substances and reduced glutathione were analyzed in heart homogenate. In isoproterenol-treated group, shrinkage of cardiac markers in serum and elevated lipid peroxidation accompanied by decreased content of reduced glutathione in heart. The prior administration of EEBSC significantly (P<0.05 prevented the isoproterenol-induced alterations and restored the cardiac markers. The observed results were further confirmed by histopathological findings. Conclusions: These findings indicate that EEBSC exerts cardioprotective effect against isoproterenol induced myocardial infarction due to its free radical scavenging effects, which maintains the tissue defence system against myocardial damage.

  14. Protective effect of catalpol on isoproterenol-induced myocardial ...

    African Journals Online (AJOL)

    ... ISO-induced cardiotoxicity in rat, by maintaining endogenous antioxidant enzyme activities and alleviating inflammatory response. This study provides novel insights that catalpol treatment could be an approach for the prevention of ischemic heart disease. Key words: Catalpol, isoproterenol, inflammation, oxidative stress, ...

  15. Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Virtanen, K.S. [First Dept. of Medicine, Helsinki Univ. Central Hospital (Finland); Nikkinen, P. [Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland); Lindroth, L. [Medix Diacor Lab. Services, Ltd., Espoo (Finland); Kuikka, J.T. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio Univ. Hospital, Univ. of Kuopio and Niuvanniemi Hospital, Kuopio (Finland)

    2002-06-01

    Aim: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. Methods: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of {sup 123}I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. Results: The more reduced post-exercise FFA metabolic rate (-63{+-}18%, mean {+-}1 SD) compared to flow (-36{+-}16%) was related to the severity of myocardial ischemia and wall motion abnormalities. Conclusion: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease. (orig.) [German] Ziel: Bei reversibler und irreversibler Myokardschaedigung infolge Ischaemie sind die Membranfunktionen der Zellen veraendert. Um myokardialen Metabolismus freier Fettsaeuren (FFA) und Durchblutung bei belastungsinduzierter Ischaemie zu vergleichen, untersuchten wir zehn Patienten mit Koronarinsuffizienz, aber ohne vorangegangenen Myokardinfarkt. Methoden: Nach Injektion von {sup 123}I-markierter Heptadekansaeure (HDA) wurde eine Serie von SPECT-Messungen nach Belastung aufgenommen. Die myokardiale Perfusion wurde abgeschaetzt durch die separat durchgefuehrte Thalliumverteilungsstudie nach Belastung. Fettsaeurestoffwechsel, Thallium-Uptake und -Washout wurden fuer die anterioren, posterioren und septalen Segmente berechnet. Ergebnisse: Eine eingeschraenktere FFA-Stoffwechselrate (-63{+-}18%, {+-}1 SD

  16. Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

    Science.gov (United States)

    Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

    2015-01-01

    We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

  17. Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction.

    Science.gov (United States)

    Nordlund, David; Kanski, Mikael; Jablonowski, Robert; Koul, Sasha; Erlinge, David; Carlsson, Marcus; Engblom, Henrik; Aletras, Anthony H; Arheden, Håkan

    2017-01-30

    Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2  = 0.92, p myocardial salvage in experimental studies.

  18. Exercise-induced silent myocardial ischemia: Evaluation by thallium-201 emission computed tomography

    International Nuclear Information System (INIS)

    Kurata, C.; Sakata, K.; Taguchi, T.; Kobayashi, A.; Yamazaki, N.

    1990-01-01

    Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent

  19. Role of Exercise Training on Autonomic Changes and Inflammatory Profile Induced by Myocardial Infarction

    Science.gov (United States)

    Rodrigues, Bruno; Lira, Fabio S.; Consolim-Colombo, Fernanda M.; Rocha, Juraci A.; Caperuto, Erico C.; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2014-01-01

    The cardiovascular autonomic imbalance in patients after myocardial infarction (MI) provides a significant increase in mortality rate, and seems to precede metabolic, hormonal, and immunological changes. Moreover, the reduction in the parasympathetic function has been associated with inflammatory response in different pathological conditions. Over the years, most of the studies have indicated the exercise training (ET) as an important nonpharmacological tool in the management of autonomic dysfunction and reduction in inflammatory profile after a myocardial infarction. In this work, we reviewed the effects of ET on autonomic imbalance after MI, and its consequences, particularly, in the post-MI inflammatory profile. Clinical and experimental evidence regarding relationship between alterations in autonomic regulation and local or systemic inflammation response after MI were also discussed. PMID:25045212

  20. Role of Exercise Training on Autonomic Changes and Inflammatory Profile Induced by Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Bruno Rodrigues

    2014-01-01

    Full Text Available The cardiovascular autonomic imbalance in patients after myocardial infarction (MI provides a significant increase in mortality rate, and seems to precede metabolic, hormonal, and immunological changes. Moreover, the reduction in the parasympathetic function has been associated with inflammatory response in different pathological conditions. Over the years, most of the studies have indicated the exercise training (ET as an important nonpharmacological tool in the management of autonomic dysfunction and reduction in inflammatory profile after a myocardial infarction. In this work, we reviewed the effects of ET on autonomic imbalance after MI, and its consequences, particularly, in the post-MI inflammatory profile. Clinical and experimental evidence regarding relationship between alterations in autonomic regulation and local or systemic inflammation response after MI were also discussed.

  1. Molecular and cellular mechanisms of cigarette smoke-induced myocardial injury: prevention by vitamin C.

    Directory of Open Access Journals (Sweden)

    Archita Das

    Full Text Available BACKGROUND: Cardiovascular disease (CVD remains one of the major killers in modern society. One strong risk factor of CVD is cigarette smoking that causes myocardial injury and leads to the genesis of pathological cardiovascular events. However, the exact toxic component(s of cigarette smoke (CS and its molecular and cellular mechanisms for causing myocardial injury leading to heart damage and its prevention are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using a guinea pig model, here we show that chronic exposure to CS produces myocardial injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C-deficient (0.5 mg/day or vitamin C-sufficient (15 mg/day diet and subjected to CS exposure from 5 Kentucky Research cigarettes (3R4F/day (6 days/week in a smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air exposure instead of CS exposure under similar conditions. Myocardial injury was produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation, apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat cardiomyocyte cells (H9c2 in vitro and guinea pigs in vivo with p-benzoquinone (p-BQ in amounts derived from CS revealed that p-BQ was a major factor responsible for CS-induced myocardial damage. A moderately large dose of vitamin C (15 mg/day prevented CS/p-BQ-induced myocardial injury. Population based studies indicated that plasma vitamin C levels of smokers without disease were significantly lower (p = 0,0000 than that of non-smokers. Vitamin C levels of CS-related cardiovascular patients were further lower (p = 0.0000 than that of smokers without disease. CONCLUSIONS/SIGNIFICANCE: The results indicate that dietary supplementation of vitamin C may be a novel and simple therapy for the prevention of pathological cardiovascular events in habitual smokers.

  2. Efficacy of gold nanoparticles against isoproterenol induced acute myocardial infarction in adult male albino rats.

    Science.gov (United States)

    Ahmed, Samah M; Abdelrahman, Shaimaa Ali; Salama, Alaa Elsayed

    2017-01-01

    This study was undertaken to investigate the role of gold nanoparticles (GNPs) of 50 nm diameter on isoproterenol (ISO) induced acute myocardial infarction in adult male albino rats. Forty five adult Wistar male albino rats were equally divided into three groups. Control (group I) was further subdivided into three subgroups. In group II, the rats received ISO subcutaneously at a dose of 100 mg/kg for three days. In group III, rats received ISO as group II and then GNPs (400 μg/kg/day) intravenously for 14 consecutive days. Echocardiography was performed. Left ventricular specimens were prepared for H&E, van Gieson staining, immunohistochemical analysis for (eNOs and Bcl-2), and Electron microscope examination. Energy dispersive X-ray microanalysis was also performed. Cardiac markers such as creatine Kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and cardiac troponin T (cTnT) were measured. Group II revealed cardiomyocytes with deeply stained acidophilic cytoplasm, small dark nuclei, intracellular vacuolations, wide intercellular spaces, and extravasated red blood cells. Increased collagen fibers were observed. Electron microscope examination showed cardiomyocyte with small and irregular outlined nuclei, mitochondria with irregular cristae and others with ruptured mitochondrial membrane, abnormal alignment of myofibrils, dilated cisternae of smooth endoplasmic reticulum, and disorganized intercalated discs. Group III showed that most cardiomyocytes preserved the normal architecture. Increased expression of eNOs immunoreaction and decreased Bcl-2 immunoreaction were detected in group II as compared to the control and GNP-treated groups. These findings suggested that GNPs of 50 nm diameter improved myocardial injury after ISO-induced myocardial infarction in rats. Myocardial infarction (MI), Isoproterenol (ISO), Nitric oxide (NO), Neuronal NOS (nNOs), Endothelial NOs (eNOs), Gold nanoparticle (GNPs), Diamiobenzidine (DAB), Serum

  3. Novel adjunctive treatments of myocardial infarction

    DEFF Research Database (Denmark)

    Schmidt, Michael Rahbek; Pryds, Kasper; Bøtker, Hans Erik

    2014-01-01

    Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve...... by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising, three follow-up studies of the effect of remote ischemic conditioning (RIC) show clinical prognostic benefit in patients undergoing coronary...... clinical outcome, but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic...

  4. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Science.gov (United States)

    Suchal, Kapil; Malik, Salma; Gamad, Nanda; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Chaudhary, Uma; Bhatia, Jagriti; Ojha, Shreesh; Arya, Dharamvir Singh

    2016-01-01

    Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway. PMID:27087891

  5. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Kapil Suchal

    2016-01-01

    Full Text Available Kaempferol (KMP, a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p. was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB, inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3, TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2. In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

  6. Myocardial oxygenation and transmural lactate metabolism during experimental acute coronary stenosis in pigs.

    Science.gov (United States)

    Gonschior, P; Gonschior, G M; Conzen, P F; Hobbhahn, J; Goetz, A E; Peter, K; Brendel, W

    1992-01-01

    Measurement of surface tissue pO2 (ptO2) with surface electrodes is increasingly applied in experimental medicine. Its use on the beating heart may seem to be problematic because transmural gradients of tissue pO2 would reduce the validity of pO2 determinations in the epicardial layers. This study attempted to determine whether ptO2 may be a valid and sensitive indicator of transmural myocardial oxygenation. In order to measure ptO2, two eight-channel Clark-type electrodes were placed on a beating porcine left ventricle (n = 13). Measurements were made at different degrees of acute stenosis of the left anterior descending artery (LAD). A 24-F cannula was inserted into the great cardiac vein, draining the poststenotic myocardium to obtain coronary venous blood samples. Transmural metabolic changes were detected simultaneously by coronary venous blood gas parameters and lactate levels. Epicardial tissue pO2 was 49 +/- 2 mm Hg (mean +/- SEM) before stenosis and decreased to a mean value of 25 +/- 2 mm Hg during stenosis. Different degrees of LAD stenosis (ptO2 range: 12-35 mm Hg) were substantial enough to alter arterio-coronary venous lactate difference (avd lactate) from +0.31 +/- 0.07 mmol/l (control) to -0.62 +/- 0.15 mmol/l (stenosis). A significant linear correlation between changes of ptO2 (delta ptO2) and changes of avd lactate (delta avd lactate) resulted (y = 0.59 + 0.62x; r = 0.86; p less than or equal to 0.001). However, linear regression analysis between delta ptO2 correlated with the corresponding data from coronary venous pO2 (delta pO2cv) oxygen content (delta O2contcv), and oxygen saturation (delta O2satcv) showed no significant correlations. We conclude that measurement of ptO2 is a sensitive and valuable indicator of transmural oxygenation in ischemic myocardium, whereas pO2cv, O2contcv and O2satcv do not seem to be valid predictors of ischemia in myocardial oxygenation.

  7. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat.

    Science.gov (United States)

    Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

    2015-01-01

    Baicalin belongs to glucuronic acid glycosides and after hydrolysis baicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat.

  8. Experimentally induced Porcine Coccidiosis | Onawunmi | Nigerian ...

    African Journals Online (AJOL)

    Journal Home > Vol 4, No 2 (1977) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Experimentally induced Porcine Coccidiosis. OA Onawunmi. Abstract. No abstract.

  9. Relation of immediate and delayed thallium-201 distribution to localization of iodine-125 antimyosin antibody in acute experimental myocardial infarction

    International Nuclear Information System (INIS)

    Khaw, B.A.; Strauss, H.W.; Pohost, G.M.; Fallon, J.T.; Katus, H.A.; Haber, E.

    1983-01-01

    Thallium-201 (TI-201) distribution in acute experimental myocardial infarction (MI) (n . 18) was compared with cardiac-specific antimyosin Fab (AM-Fab) uptake, a specific marker for myocardial necrosis. When antimyosin was injected 4 hours after ligation with TI-201 administered 23 hours 55 minutes later and measurement of myocardial distribution determined 5 minutes after intravenous administration of TI-201, (1) TI-201 distribution closely correlated with microsphere regional blood flow, and (2) an inverse exponential relation to iodine-125 (I-125) AM-Fab uptake was apparent. In another group of 4 animals, TI-201 and AM-Fab were administered intravenously 4 hours after MI, and 36 hours later myocardial distribution was measured. This delayed TI-201 distribution had a close inverse linear correlation with I-125 AM-Fab uptake. This inverse linear relation also was apparent in 28-hour-old MIs in dogs (n . 4) where collateral circulation had been established. TI-201 was administered intravenously at 27 hours after MI, and TI-201 distribution was determined 1 hour later. The present study demonstrated that whereas immediate TI-201 distribution is flow-limited, delayed TI-201 distribution is a marker of cell viability which, due to prolonged circulation time and redistribution, is not flow-limited

  10. Case Report: Hypoglycaemia-induced myocardial infarction as a result of sulphonylurea misuse.

    LENUS (Irish Health Repository)

    Corley, B T

    2010-12-24

    Background  Recent large-scale randomized trials of intensive therapy in Type 2 diabetes have reported increased cardiovascular morbidity and mortality in patient populations who experience a high frequency of hypoglycaemic events. However, there are few descriptions of hypoglycaemia leading directly to a myocardial infarct in the medical literature to date. Case report  In this article we describe the case of a 76-year-old woman without diabetes who presented with symptoms, left bundle branch block and raised troponin, indicative of a myocardial infarction. She was also noted to be hypoglycaemic with a plasma glucose level of 2.5 mmol\\/l. It was subsequently discovered that she had mistakenly been dispensed glibenclamide, a long-acting sulphonylurea, in the preceding weeks. Her cardiac symptoms resolved completely upon treatment of her hypoglycaemia and she had no significant coronary artery disease on angiography. Conclusion  This is the first case of sulphonylurea-induced myocardial infarct in a patient without diabetes and illustrates the adverse effects of acute hypoglycaemia upon the cardiovascular system.

  11. High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size.

    Science.gov (United States)

    Bourdier, Guillaume; Flore, Patrice; Sanchez, Hervé; Pepin, Jean-Louis; Belaidi, Elise; Arnaud, Claire

    2016-01-15

    Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients. Copyright © 2016 the American Physiological Society.

  12. Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

    International Nuclear Information System (INIS)

    Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko

    1998-01-01

    Reversible thallium-201 ( 201 Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201 Tl and rest 123 I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201 Tl in 19/28 patients with HCM. 123 I-BMIPP uptake was decreased compared with delayed 201 Tl in 106/364 (29%) of the total myocardial segments (p 123 I-BMIPP and 201 Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201 Tl defects (p 123 I-BMIPP and 201 Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

  13. The causes and clinical significance of exercise-induced silent myocardial ischemia evaluated by ischemic range and intensity with exercise Tl-201 myocardial SPECT

    International Nuclear Information System (INIS)

    Moriai, Naoki; Nakai, Kenji; Hiramori, Katsuhiko

    1992-01-01

    We investigated the causes and long-term prognosis of exercise-induced silent myocardial ischemia (SMI) by means of exercise Tl-201 myocardial SPECT (Ex-SPECT) in 97 patients with effort angina or old myocardial infarction (OMI). These patients were proven to have significant stenosis by coronary angiography. The subjects were divided into three groups based on the presence or absence of Tl-201 redistribution (RD) or angina during exercise testing. Group one consisted of 34 patients who had RD on Ex-SPECT and angina during exercise testing: the painful myocardial ischemia (PMI) group. The second group consisted of 38 patients who had RD on Ex-SPECT, but no angina during exercise testing: the SMI group. The third group consisted of 25 patients who had no RD: the RD (-) group. The ischemic range and intensity were quantified by the defect volume ratio (DVR) and defect severity index (DSI), respectively. Comparison of the DVR and DSI values for the PMI and SMI groups revealed that the DVR and DSI values for the SMI group were lower than those of the PMI group. Also the prognosis of the SMI group tended to be worse than that of the RD (-) group. Thus, we concluded that the SMI and PMI groups should receive identical treatment. (author)

  14. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de, E-mail: erosaa@cardiol.br [Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2015-02-15

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABA{sub B} receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABA{sub B} receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABA{sub B} receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  15. Inflammatory response to mental stress and mental stress induced myocardial ischemia.

    Science.gov (United States)

    Hammadah, Muhammad; Sullivan, Samaah; Pearce, Brad; Al Mheid, Ibhar; Wilmot, Kobina; Ramadan, Ronnie; Tahhan, Ayman Samman; O'Neal, Wesley T; Obideen, Malik; Alkhoder, Ayman; Abdelhadi, Naser; Mohamed Kelli, Heval; Ghafeer, Mohamad Mazen; Pimple, Pratik; Sandesara, Pratik; Shah, Amit J; Hosny, Kareem Mohammed; Ward, Laura; Ko, Yi-An; Sun, Yan V; Weng, Lei; Kutner, Michael; Bremner, J Douglas; Sheps, David S; Esteves, Fabio; Raggi, Paolo; Vaccarino, Viola; Quyyumi, Arshed A

    2018-02-01

    Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. Of 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p mental stress were significantly associated with MSIMI. Results in the replication sample were similar. Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI. Copyright © 2017. Published by Elsevier Inc.

  16. Exercise myocardial perfusion imaging to evaluate inducible ischaemia in children with Kawasaki disease.

    Science.gov (United States)

    Kashyap, Raghava; Mittal, Bhagwant Rai; Bhattacharya, Anish; Manojkumar, Rohit; Singh, Surjit

    2011-02-01

    Kawasaki disease (KD) is an acute multi-system vasculitis of unknown aetiology, which occurs predominantly in infants and young children. Coronary artery abnormalities may occur in 15-25% of patients who are not treated in the acute phase of the disease with a high dose of intravenous immunoglobulin. Myocardial perfusion imaging is used as a modality to monitor the cardiovascular effects of the disease. The objective of our study was to assess the feasibility and results of exercise myocardial perfusion scintigraphy in children with Kawasaki disease. We performed stress myocardial perfusion imaging in 84 patients suffering from KD. The diagnosis of KD was based on the criteria laid down by the American Heart Association. Myocardial perfusion imaging was performed using either thallium or technetium-99m tetrofosmin. Physical exercise using the Bruce protocol was the most frequent cardiac stressor (74 patients) whereas in few patients (seven patients) dobutamine was used to increase the heart rate. Stress-induced reversible perfusion defects were found only in 12 of the total number of patients. Among these two had coronary artery abnormalities on echocardiography. Four of these patients had achieved adequate heart rate with stress. Two among these patients had a repeat imaging done after 1 year and the perfusion defects showed complete resolution in them. This study thus suggests that reversible perfusion defects are seen in asymptomatic patients with KD and that the presence of perfusion defects may not be associated with echocardiographic demonstration of coronary abnormalities. The treadmill test is a reasonable stress protocol for these patients.

  17. Radiation-induced myocardial perfusion abnormalities in breast cancer patients following external beam radiation therapy

    Directory of Open Access Journals (Sweden)

    Mohammad Eftekhari

    2015-01-01

    Full Text Available Objective(s: Radiation therapy for breast cancer can induce myocardial capillary injury and increase cardiovascular morbidity and mortality. A prospective cohort was conducted to study the prevalence of myocardial perfusion abnormalities following radiation therapy of left-sided breast cancer patients as compared to those with right–sided cancer. Methods: To minimize potential confounding factors, only those patients with low 10-year risk of coronary artery disease (based on Framingham risk scoring were included. All patients were initially treated by modified radical mastectomy and then were managed by postoperative 3D Conformal Radiation Therapy (CRT to the surgical bed with an additional 1-cm margin, delivered by 46-50 Gy (in 2 Gy daily fractions over a 5-week course. The same dose-adjusted chemotherapy regimen (including anthracyclines, cyclophosphamide and taxol was given to all patients. Six months after radiation therapy, all patients underwent cardiac SPECT for the evaluation of myocardial perfusion. Results: A total of 71 patients with a mean age of 45.3±7.2 years [35 patients with leftsided breast cancer (exposed and 36 patients with right-sided cancer (controls] were enrolled. Dose-volume histogram (DVH [showing the percentage of the heart exposed to >50% of radiation] was significantly higher in patients with left-sided breast cancer. Visual interpretation detected perfusion abnormalities in 42.9% of cases and 16.7% of controls (P=0.02, Odds ratio=1.46. In semiquantitative segmental analysis, only apical (28.6% versus 8.3%, P=0.03 and anterolateral (17.1% versus 2.8%, P=0.049 walls showed significantly reduced myocardial perfusion in the exposed group. Summed Stress Score (SSS of>3 was observed in twelve cases (34.3%, while in five of the controls (13.9%,(Odds ratio=1.3. There was no significant difference between the groups regarding left ventricular ejection fraction. Conclusion: The risk of radiation induced myocardial

  18. The triterpenoids of Ganoderma tsugae prevent stress-induced myocardial injury in mice.

    Science.gov (United States)

    Kuok, Qian-Yu; Yeh, Chen-Yu; Su, Bor-Chyuan; Hsu, Pei-Ling; Ni, Hao; Liu, Ming-Yie; Mo, Fan-E

    2013-10-01

    Ganoderma mushrooms (Lingzhi in Chinese) have well-documented health benefits. Ganoderma tsugae (G. tsugae), one of the ganoderma species, has been commercially cultivated as a dietary supplement. Because G. tsugae has high antioxidant activity and because oxidative stress is often associated with cardiac injury, we hypothesized that G. tsugae protects against cardiac injury by alleviating oxidative stress. We tested the hypothesis using a work-overload-induced myocardial injury model created by challenging mice with isoproterenol (ISO). Remarkably, oral G. tsugae protected the mice from ISO-induced myocardial injury. Moreover, the triterpenoid fraction of G. tsugae, composed of a mixture of nine structurally related ganoderic acids (GAs), provided cardioprotection by inhibiting the ISO-induced expression of Fas/Fas ligand, oxidative stress, and apoptosis. The antioxidant activity of GAs was tested in cultured cardio-myoblast H9c2 cells against the insult of H₂O₂. GAs dissipated the cellular reactive oxygen species imposed by H₂O₂ and prevented cell death. Our findings uncovered the cardioprotective activity of G. tsugae and identified GAs as the bioactive components against cardiac insults. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Dietary Fatty Acids Alter Lipid Profiles and Induce Myocardial Dysfunction without Causing Metabolic Disorders in Mice.

    Science.gov (United States)

    Chen, Bainian; Huang, Yifan; Zheng, Dong; Ni, Rui; Bernards, Mark A

    2018-01-19

    Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and myocardial dysfunction. We investigated whether, without causing metabolic disorders, the uptake of individual dietary SFA species alters lipid profiles and induces myocardial dysfunction. C57BL/6 mice were fed various customized long-chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD), cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An isocaloric fat diet, containing medium-chain triglycerides, served as a control (CHD). Long-term intake of dietary long-chain SFA differentially affected the fatty acid composition in cardiac phospholipids. All long-chain SFA diets increased the levels of arachidonic acid and total SFA in cardiac phospholipids. The preferential incorporation of individual SFA into the cardiac phospholipid fraction was dependent on the dietary SFA species. Cardiac ceramide content was elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only presented in mice fed HMD or HPD. We have demonstrated that the intake of long-chain SFA species differentially alters cardiac lipid profiles and induces cardiac dysfunction, without causing remarkable metabolic disorders.

  20. Experimentally-induced dissociation impairs visual memory.

    Science.gov (United States)

    Brewin, Chris R; Mersaditabari, Niloufar

    2013-12-01

    Dissociation is a phenomenon common in a number of psychological disorders and has been frequently suggested to impair memory for traumatic events. In this study we explored the effects of dissociation on visual memory. A dissociative state was induced experimentally using a mirror-gazing task and its short-term effects on memory performance were investigated. Sixty healthy individuals took part in the experiment. Induced dissociation impaired visual memory performance relative to a control condition; however, the degree of dissociation was not associated with lower memory scores in the experimental group. The results have theoretical and practical implications for individuals who experience frequent dissociative states such as patients with posttraumatic stress disorder (PTSD). Copyright © 2013 Elsevier Inc. All rights reserved.

  1. beta-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction.

    Science.gov (United States)

    Paiva, Sergio A R; Novo, Rosangela; Matsubara, Beatriz B; Matsubara, Luiz S; Azevedo, Paula S; Minicucci, Marcos F; Campana, Alvaro O; Zornoff, Leonardo A M

    2005-09-01

    The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary beta-carotene (BC), on ventricular remodeling and survival after myocardial infarction (MI). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n = 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 100 g were administered one of the treatments until they weighed 200 to 250 g (approximately 5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation.

  2. Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography.

    Science.gov (United States)

    Cherubini, Antonella; Cioffi, Giovanni; Mazzone, Carmine; Faganello, Giorgio; Barbati, Giulia; Tarantini, Luigi; Russo, Giulia; Stefenelli, Carlo; Humar, Franco; Grande, Eliana; Fisicaro, Maurizio; Pandullo, Claudio; Di Lenarda, Andrea

    2016-06-01

    Tissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk. Two hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise. ExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S') was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S', higher LV circumferential end-systolic stress and LASF. In asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

  3. Troponin T and Histological Characteristics of Rat Myocardial Infarction Induced by Isoproterenol

    Directory of Open Access Journals (Sweden)

    Sabaheta Hasić

    2007-08-01

    Full Text Available In our investigation, we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP. We investigated cardiac troponin T blood level (cTnT and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12. Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g and ISP II (BW 250-400g. Control group (n=9 was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA sandwich immunoassay in rat serum 4 hours after ISP application. Rats’ hearts were dissected and examined by qualitative histological method (HE. Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001 vs. control and ISP I (p<0,05 vs. control. Significant difference was beetween ISP I and ISP II subgroups (p<0.001. The accent of histological changes of myocardium was on nuclei of cell. Cells showed acydophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different beetween ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Suben-docardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis.

  4. MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy

    Science.gov (United States)

    Pan, Wei; Zhong, Yun; Cheng, Chuanfang; Liu, Benrong; Wang, Li; Li, Aiqun; Xiong, Longgen; Liu, Shiming

    2013-01-01

    Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (operation group). Cardiomyocyte autophagy was enhanced in rats from the operation group, compared with those in the sham operation group. Moreover, the operation group showed up-regulation of beclin-1 (an autophagy-related gene), and down-regulation of miR-30 in cardiac tissue. The effects of inhibition and over-expression of the beclin-1 gene on the expression of hypertrophy-related genes and on autophagy were assessed. Angiotensin II-induced myocardial hypertrophy was found to be mediated by over-expression of the beclin-1 gene. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. miR-30a induced alterations in beclin-1 gene expression and autophagy in cardiomyocytes. Treatment of cardiomyocytes with miR-30a mimic attenuated the Angiotensin II-induced up-regulation of hypertrophy-related genes and decreased in the cardiomyocyte surface area. Conversely, treatment with miR-30a inhibitor enhanced the up-regulation of hypertrophy-related genes and increased the surface area of cardiomyocytes induced by Angiotensin II. In addition, circulating miR-30 was elevated in patients with left ventricular hypertrophy, and circulating miR-30 was positively associated with left ventricular wall thickness. Collectively, these above-mentioned results suggest that Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. Circulating miR-30 may be an important marker for the diagnosis of left ventricular hypertrophy. PMID:23326547

  5. Sex Differences in Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Heart Disease.

    Science.gov (United States)

    Vaccarino, Viola; Wilmot, Kobina; Al Mheid, Ibhar; Ramadan, Ronnie; Pimple, Pratik; Shah, Amit J; Garcia, Ernest V; Nye, Jonathon; Ward, Laura; Hammadah, Muhammad; Kutner, Michael; Long, Qi; Bremner, J Douglas; Esteves, Fabio; Raggi, Paolo; Quyyumi, Arshed A

    2016-08-24

    Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress-induced myocardial ischemia (MSIMI). We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent (99m)Tc-sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more-adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, Pstress. Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  6. “Spice” (Synthetic Marijuana Induced Acute Myocardial Infarction: A Case Series

    Directory of Open Access Journals (Sweden)

    E. Ul Haq

    2017-01-01

    Full Text Available Marijuana is the most widely abused “recreational” substance in the United States, with highest prevalence in young adults. It is reported to cause ischemic strokes, hepatitis, anxiety, and psychosis. Although it is associated with dose dependent tachycardia and can lead to coronary vasospasm, it has not been directly related to acute myocardial infarction (AMI. Marijuana induced coronary vasospasm can result in endothelial denudation at the site of a vulnerable atherosclerotic plaque in response to hemodynamic stressors, potentially causing an AMI. Spice refers to herbal mixture with composition and effects similar to that of marijuana and therefore is referred to as “synthetic marijuana.” Herein, we report 3 cases of spice induced ST-segment elevation myocardial infarction. All patients were relatively young and had few or absolutely no risk factors for cardiovascular disease. All patients underwent emergent coronary angiography, with two needing stent placement and the third requiring only aspiration thrombectomy. Our case series emphasizes the importance of suspecting and investigating synthetic marijuana use in low risk young adults presenting with AMI.

  7. An experimental study on the acute myocardial infarction with CT perfusion scans

    International Nuclear Information System (INIS)

    Liu Yuanjian; Yan Weiqiang; Wang Chenglin; Liu Pengcheng; Feng Xiaoyuan; Shen Tianzhen; Chen Xingrong

    2004-01-01

    Objective: To determine the reliability of CT perfusion scans and its parameters of γ-variate curve in evaluating the acute myocardial infarction for clinical reference of diagnosis on coronary artery disease and myocardial infarction. Methods: Imatron C-150 electron beam CT (EBCT) were used to scan a hydrodynamic model which could mimic a change of contrast medium by intravenous injection in vivo. Then 6 adult canines were employed in the experiment with thoracic operation, and branches of the anterior descending and circumflex of left coronary arteries (LCA) were ligated so that myocardial infarction was made out. After intravenous administration of contrast medium, the hearts were scanned with perfusion EBCT and γ-variate curves were manifested. Some heterogeneities and differentiations between the normality and the infarctions were put forward when the parameters of all these curves were analyzed and statistically processed. Two myocardial infarctions were also verified by SPECT, and all the samples stained with TTC method were compared with those on the perfusion images. The pathological study with optical microscope and electron microscope were further carried on. Results: The ascending slopes of γ-variate curves were different in the perfusion quantity. The normal curve of canine myocardium showed a somewhat quick ascending pattern first, and then a gradual descending pattern successively, with the ascending time of about 10-13 s, ascending CT value of about 34-37 HU, and peak CT value of about 70-81 HU. Whereas the curve on myocardial infarction demonstrated a prolonged ascending time of about 19.9 s, diminished ascending CT value of only about 20 HU, and peak CT value of about 53.8 HU, which were significantly different from the normality (P<0.05). Conclusion: There are some differences in γ-variate curves between normal myocardium and myocardial infarction, which can be detected by CT perfusion scan. (authors)

  8. Nitric oxide treatments as adjuncts to reperfusion in acute myocardial infarction: a systematic review of experimental and clinical studies.

    Science.gov (United States)

    Bice, Justin S; Jones, Bethan R; Chamberlain, Georgia R; Baxter, Gary F

    2016-03-01

    Unmodified reperfusion therapy for acute myocardial infarction (AMI) is associated with irreversible myocardial injury beyond that sustained during ischemia. Studies in experimental models of ischemia/reperfusion and in humans undergoing reperfusion therapy for AMI have examined potential beneficial effects of nitric oxide (NO) supplemented at the time of reperfusion. Using a rigorous systematic search approach, we have identified and critically evaluated all the relevant experimental and clinical literature to assess whether exogenous NO given at reperfusion can limit infarct size. An inclusive search strategy was undertaken to identify all in vivo experimental animal and clinical human studies published in the period 1990-2014 where NO gas, nitrite, nitrate or NO donors were given to ameliorate reperfusion injury. Articles were screened at title and subsequently at abstract level, followed by objective full text analysis using a critical appraisal tool. In twenty-one animal studies, all NO treatments except nitroglycerin afforded protection against measures of reperfusion injury, including infarct size, creatinine kinase release, neutrophil accumulation and cardiac dysfunction. In three human AMI RCT's, there was no consistent evidence of infarct limitation associated with NO treatment as an adjunct to reperfusion. Despite experimental evidence that most NO treatments can reduce infarct size when given as adjuncts to reperfusion, the value of these interventions in clinical AMI is unproven. Our study raises issues for the design of further clinical studies and emphasises the need for improved design of animal studies to reflect more accurately the comorbidities and other confounding factors seen in clinical AMI.

  9. CO inhalation at dose corresponding to tobacco smoke worsens cardiac remodeling after experimental myocardial infarction in rats.

    Science.gov (United States)

    Mirza, Alain; Eder, Véronique; Rochefort, Gaël Y; Hyvelin, Jean-Marc; Machet, Marie Christine; Fauchier, Laurent; Bonnet, Pierre

    2005-06-01

    We hypothesized that inhalation of carbon monoxide (CO) (500 ppm), similar to that in tobacco smoke, disturbs the cardiovascular adaptation after myocardial infarction by increasing remodeling. Four groups of rats were assessed. Two groups had myocardial infarction induced by the ligation of the left coronary artery: the first group was exposed to air (infarcted air group, n = 12), and the second was exposed to CO (infarcted CO group, n = 11). They were compared to two sham-operated groups, a control air group (n = 10), and a control CO group (n = 7) exposed (3 weeks) to CO. Aerobic endurance capacity was assessed in both the infarct CO and infarct air group (endurance capacity = 0.043 +/- 0.006 m.min(-1).g(-1) vs. 0.042 +/- 0.005 m.min(-1).g(-1), not significant). In the infarcted CO group compared to the infarcted air group, the dilatation of the left ventricle observed 3 weeks after infarction was increased, (left ventricular diastolic (LVD) diameter (D) = 9 +/- 0.4 vs. 7 +/- 0.4 mm, p infarcted CO group, the infarct size increased. Echocardiography and histology showed hypertrophy of the contralateral wall similar to that observed in the noninfarcted control CO group. In conclusion, chronic CO inhalation worsens heart failure in rats with myocardial infarction by an increase in the infarct size and hypertrophy remodeling.

  10. The past, the present and the future of experimental research on myocardial ischemia and protection

    Czech Academy of Sciences Publication Activity Database

    Ošťádal, Bohuslav

    2009-01-01

    Roč. 61, č. 1 (2009), s. 3-12 ISSN 1734-1140 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardial ischemia * protection * cell death Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery Impact factor: 2.086, year: 2009

  11. Baroreflex deficiency induces additional impairment of vagal tone, diastolic function and calcium handling proteins after myocardial infarction

    Science.gov (United States)

    Mostarda, Cristiano; Rodrigues, Bruno; Medeiros, Alessandra; Moreira, Edson D; Moraes-Silva, Ivana C; Brum, Patricia C; Angelis, Katia De; Irigoyen, Maria-Cláudia

    2014-01-01

    Baroreflex dysfunction has been considered an important mortality predictor after myocardial infarction (MI). However, the impact of baroreflex deficiency prior to MI on tonic autonomic control and cardiac function, and on the profile of proteins associated with intracellular calcium handling has not yet been studied. The aim of the present study was to analyze how the impairment of baroreflex induced by sinoaortic denervation (SAD) prior to MI in rats affects the tonic autonomic control, ventricular function and cardiomyocyte calcium handling proteins. After 15 days of following or SAD surgery, rats underwent MI. Echocardiographic, hemodynamic, autonomic and molecular evaluations were performed 90 days after MI. Baroreflex impairment led to additional damage on: left ventricular remodeling, diastolic function, vagal tonus and intrinsic heart rate after MI. The loss of vagal component of the arterial baroreflex and vagal tonus were correlated with changes in the cardiac proteins involved in intracellular calcium homeostasis. Furthermore, additional increase in sodium calcium exchanger expression levels was associated with impaired diastolic function in experimental animals. Our findings strongly suggest that previous arterial baroreflex deficiency may induce additional impairment of vagal tonus, which was associated with calcium handling proteins abnormalities, probably triggering ventricular diastolic dysfunction after MI in rats. PMID:24936224

  12. Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease.

    Science.gov (United States)

    Jiang, Wei; Samad, Zainab; Boyle, Stephen; Becker, Richard C; Williams, Redford; Kuhn, Cynthia; Ortel, Thomas L; Rogers, Joseph; Kuchibhatla, Maragatha; O'Connor, Christopher; Velazquez, Eric J

    2013-02-19

    The goal of this study was to evaluate the prevalence and clinical characteristics of mental stress-induced myocardial ischemia. Mental stress-induced myocardial ischemia is prevalent and a risk factor for poor prognosis in patients with coronary heart disease, but past studies mainly studied patients with exercise-induced myocardial ischemia. Eligible patients with clinically stable coronary heart disease, regardless of exercise stress testing status, underwent a battery of 3 mental stress tests followed by a treadmill test. Stress-induced ischemia, assessed by echocardiography and electrocardiography, was defined as: 1) development or worsening of regional wall motion abnormality; 2) left ventricular ejection fraction reduction ≥ 8%; and/or 3) horizontal or downsloping ST-segment depression ≥ 1 mm in 2 or more leads lasting for ≥ 3 consecutive beats during at least 1 mental test or during the exercise test. Mental stress-induced ischemia occurred in 43.45%, whereas exercise-induced ischemia occurred in 33.79% (p = 0.002) of the study population (N = 310). Women (odds ratio [OR]: 1.88), patients who were not married (OR: 1.99), and patients who lived alone (OR: 2.24) were more likely to have mental stress-induced ischemia (all p stress-induced ischemia (all p stress-induced ischemia is more common than exercise-induced ischemia in patients with clinically stable coronary heart disease. Women, unmarried men, and individuals living alone are at higher risk for mental stress-induced ischemia. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Correlation between left ventricular filling and ischemic extent during exercise-induced myocardial ischemia

    International Nuclear Information System (INIS)

    Ando, Akitada; Yokota, Mitsuhiro; Iwase, Mitsunori

    1993-01-01

    The aim of this study was to determine how the extent of exercise-induced myocardial ischemia influence left ventricular filling. Twenty-two consecutive patients with effort angina, consisting of 16 with single vessel disease and 6 with double vessel disease, underwent exercise studies in lying and sitting positions. Extent score (ES) and severity score (SS) were calculated on polar map prepared from early exercise Tl-201 myocardial SPECT images to determine ischemic extent. Pulmonary arterial wedge pressure (PAWP), as obtained at exercise in lying position, correlated significantly well with both ES (r=0.75, p<0.001) and SS (r=0.61, p<0.01). There was, however, no significant correlation between the other hemodynamic parameters, such as heart rate, systolic pressure, rate-pressure product, cardiac index and stroke index, and both ES and SS. Either increased PAWP or ischemic extent was not dependent on the number of diseased vessels. In conclusion, the extent of increased left ventricular filling did not correlate with the number of diseased vessels, but correlated positively with ischemic extent. (N.K.)

  14. Cardioprotective effect of hydroalcoholic extract of Tecoma stans flowers against isoproterenol induced myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Shanmukha Ittagi

    2014-02-01

    Full Text Available Objective: To investigate the cardioprotective effect of 70% ethanolic extract of Tecoma stans (T. stans flowers against isoproterenol-induced myocardial infarction in rat myocardium. Methods: Wister rats were pretreated with 70% ethanolic extract of T. stans flowers (250 and 500 mg/kg orally for 14 d and then intoxicated with isoproterenol [200 mg/(kg · day, s.c.] for 2 consecutive d. The biochemical markers for myocardial infarction such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, total cholesterol, triglycerides, low density lipoproteins and high density lipoproteins were determined. In addition the antioxidant status on heart tissue is also evaluated by testing the activities of antioxidant enzymes such as lipid peroxidation, superoxide dismutase, reduced glutathione and catalase. Results: The results indicated that pretreatment with 70% ethanolic extract of T. stans flowers prevented fall in antioxidants and retarded elevation of cardiac damage markers in isoproterenol treated rats, significantly. In addition, these findings were evidently supported by the remarkable protection revealed in the histopathological studies, even GC-MS analysis data also substantiated out investigation. Conclusions: It was concluded that, in addition to poly phenolics, some of the phyto fragments found during GC-MS analysis might also contributed to the cardiac protection offered by the extract.

  15. A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

    Science.gov (United States)

    Shi, Weiwei; McIver, Bryant V; Kalra, Kanika; Sarin, Eric L; Schmarkey, Susan; Duggan, Michael; Thourani, Vinod H; Guyton, Robert A; Padala, Muralidhar

    2017-08-01

    Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

  16. Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

    Science.gov (United States)

    Spaulding, Kimberly; Takaba, Kiyoaki; Collins, Alexander; Faraji, Farshid; Wang, Guanying; Aguayo, Esteban; Ge, Liang; Saloner, David; Wallace, Arthur W; Baker, Anthony J; Lovett, David H; Ratcliffe, Mark B

    2018-01-01

    Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; pborder zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.

  17. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    Science.gov (United States)

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic PreconditioningCraig...

  18. Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats

    NARCIS (Netherlands)

    Ouwens, D.M.; de Boer, C.; Fodor, M.; Galan, P.; Heine, R.J.; Maassen, J.A.; Diamant, M.

    2005-01-01

    Aims/hypothesis: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic

  19. Diagnosis of myocardial infarction based on lectin-induced erythrocyte agglutination: a feasibility study

    Science.gov (United States)

    Bocsi, József; Nieschke, Kathleen; Mittag, Anja; Reichert, Thomas; Laffers, Wiebke; Marecka, Monika; Pierzchalski, Arkadiusz; Piltz, Joachim; Esche, Hans-Jürgen; Wolf, Günther; Dähnert, Ingo; Baumgartner, Adolf; Tarnok, Attila

    2014-03-01

    Myocardial infarction (MI) is an acute life-threatening disease with a high incidence worldwide. Aim of this study was to test lectin-carbohydrate binding-induced red blood cell (RBC) agglutination as an innovative tool for fast, precise and cost effective diagnosis of MI. Five lectins (Ricinus communis agglutinin (RCA), Phaseolus vulgaris erythroagglutinin (PHA), Datura stramonium agglutinin (DSA), Artocarpus agglutinin (ArA), Triticum agglutinin (TA)) were tested for ability to differentiate between agglutination characteristics in patients with MI (n = 101) or angina pectoris without MI (AP) (n = 34) and healthy volunteers (HV) as control (n =68) . RBC agglutination was analyzed by light absorbance of a stirred RBC suspension in the green to red light spectrum in an agglutimeter (amtec, Leipzig, Germany) for 15 min after lectin addition. Mean cell count in aggregates was estimated from light absorbance by a mathematical model. Each lectin induced RBC agglutination. RCA led to the strongest RBC agglutination (~500 RBCs/aggregate), while the others induced substantially slower agglutination and lead to smaller aggregate sizes (5-150 RBCs/aggregate). For all analyzed lectins the lectin-induced RBC agglutination of MI or AP patients was generally higher than for HV. However, only PHA induced agglutination that clearly distinguished MI from HV. Variance analysis showed that aggregate size after 15 min. agglutination induced by PHA was significantly higher in the MI group (143 RBCs/ aggregate) than in the HV (29 RBC-s/aggregate, p = 0.000). We hypothesize that pathological changes during MI induce modification of the carbohydrate composition on the RBC membrane and thus modify RBC agglutination. Occurrence of carbohydrate-lectin binding sites on RBC membranes provides evidence about MI. Due to significant difference in the rate of agglutination between MI > HV the differentiation between these groups is possible based on PHA-induced RBC-agglutination. This novel assay

  20. Outcome of Patients With Adenosine-Induced ST Segment Depression and Normal Myocardial Perfusion

    International Nuclear Information System (INIS)

    El-Refaei, S.; Selim, M.

    2011-01-01

    The aim of the present study was to determine the outcome of patients with normal MPS and adenosine-induced ST segment depression. A total of 1867 patients underwent adenosine Tc99m-tetrofosmin MPS in nuclear medicine unit in Saudi German Hospital, Saudi Arabia, between January 2004 and May 2008. Their ECGs were checked for ST segment depression during adenosine infusion. All patients with ≥ 1 mm horizontal or down-sloping ST segment depression or≥ 1.5 mm up-sloping ST segment depression were included in the study. Fifty-six patients met our inclusion criteria, of which 45 (80%) were females. During the follow-up period, a total of 15 of patients ended up doing coronary angiography, either for high clinical suspicion or following a second positive MPS performed 6-18 months after the first study. Seven of them were positive for coronary artery disease and were subsequently treated with revascularization procedure, and 8 returned either normal angiography or non-obstructive coronary artery disease. Male diabetic smoking patients were more prevalent and underwent revascularization. The patients were followed up for a mean of 22.8 ±7.8 months. No cardiac deaths or myocardial infarctions were reported. It could be concluded that adenosine-induced ST segment depression in patients with normal myocardial perfusion was a benign finding and did not increase the very low risk of cardiac events in those patients. However, male smokers and/or diabetics might need further investigation. This suggestion needs further evaluation

  1. Cardioprotective potential of Punica granatum extract in isoproterenol-induced myocardial infarction in Wistar rats.

    Science.gov (United States)

    Mohan, Mahalaxmi; Patankar, Pankaj; Ghadi, Prakash; Kasture, Sanjay

    2010-01-01

    To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

  2. Neutrophil accumulation in experimental myocardial infarcts: relation with extent of injury and effect of reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Chatelain, P.; Latour, J.G.; Tran, D.; de Lorgeril, M.; Dupras, G.; Bourassa, M.

    1987-05-01

    The effects of reperfusion on the myocardial accumulation of neutrophils and their role in the extent of injury were investigated in a canine preparation with a 3 hr coronary occlusion followed by 21 hr of reperfusion. The left anterior descending coronary artery (LAD) was permanently occluded in group 1 and reperfused after 3 hr in four others (groups 2 to 5). All but group 5 received lidocaine (1 mg/min over 8 hr). A critical stenosis was produced and left in place at reperfusion only in group 2. In groups 1 and 2, /sup 111/In-labeled autologous neutrophils were injected at the time of coronary occlusion. Group 4 animals were rendered leukopenic 2 hr before the coronary ligature and throughout the experiment by injection of an antineutrophil rabbit serum. Quantification of the radioactivity by digitized scintigraphy of the heart slices revealed an 80% increase in neutrophil accumulation in the infarct region after reperfusion (group 2) as compared with permanent occlusion (group 1). Gamma counting of myocardial tissue samples showed that the neutrophil accumulation ratio in the subendocardial central zone of the infarct was increased five times by reperfusion, whereas no difference was evident in the subepicardium. Infarct size and myocardial area at risk were not statistically different among the five groups. However LAD flow in the leukopenic group (group 4) was significantly higher 30 min after reperfusion (40.0 +/- 5 ml/min) when compared with the preocclusion value (21.7 +/- 4 ml/min). In contrast, in a parallel experiment without leukopenia (group 3), LAD flow after reperfusion did not differ from the preocclusion value.

  3. Protection against isoproterenol-induced myocardial necrosis in rats by 6-mercaptopurine and 6-thioguanine or by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, X.; Balazs, T.

    1989-03-01

    Isoproterenol produces myocardial necrosis in rats. To investigate the possible role of oxygen free radicals generated by xanthine oxidase and neutrophils, we examined the effects of the xanthine oxidase inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG) combined and allopurinol, or of irradiation (to induce leukopenia) on isoproterenol-induced myocardial necrosis (ISOMN). The incidence and severity of ISOMN was significantly reduced by 6MP + 6TG but not by the specific inhibitor of xanthine oxidase, allopurinol, indicating that the protective effects of 6MP + 6TG may be due to its free radical scavenging activity rather than its xanthine oxidase inhibitory activity. Irradiation provided complete protection against ISOMN in all rats. Marked leukopenia or other radiation-induced protective factors could play a role in the mechanism of the protection.

  4. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard

    2012-01-01

    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation...... and its response to hypoxic stress. To this end, we examined Apoe(-/-) mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2) in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling...

  5. Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease.

    Science.gov (United States)

    Boyle, Stephen H; Samad, Zainab; Becker, Richard C; Williams, Redford; Kuhn, Cynthia; Ortel, Thomas L; Kuchibhatla, Maragatha; Prybol, Kevin; Rogers, Joseph; O'Connor, Christopher; Velazquez, Eric J; Jiang, Wei

    2013-01-01

    The aim of this study was to examine the associations between depressive symptoms and mental stress-induced myocardial ischemia (MSIMI) in patients with coronary heart disease (CHD). Adult patients with documented CHD were recruited for baseline mental stress and exercise stress screening testing as a part of the enrollment process of the Responses of Myocardial Ischemia to Escitalopram Treatment trial. Patients were administered the Beck Depression Inventory II and the Center for Epidemiologic Studies Depression Scale. After a 24-48-hour β-blocker withdrawal, participants completed three mental stress tests followed by a treadmill exercise test. Ischemia was defined as a) any development or worsening of any wall motion abnormality and b) reduction of left ventricular ejection fraction at least 8% by transthoracic echocardiography and/or ischemic ST-segment change by electrocardiography during stress testing. MSIMI was considered present when ischemia occurred in at least one mental test. Data were analyzed using logistic regression adjusting for age, sex, and resting left ventricular ejection fraction. One hundred twenty-five (44.2%) of 283 patients were found to have MSIMI, and 93 (32.9%) had ESIMI. Unadjusted analysis showed that Beck Depression Inventory II scores were positively associated with the probability of MSIMI (odds ratio = 0.1.30: 95% confidence interval = 1.06-1.60, p = .013) and number of MSIMI-positive tasks (all p < .005). These associations were still significant after adjustment for covariates (p values <.05). In patients with CHD, depressive symptoms were associated with a higher probability of MSIMI. These observations may enhance our understanding of the mechanisms contributing to the association of depressive symptoms to future cardiovascular events. Trial Registration Clinicaltrials.gov identifier: NCT00574847.

  6. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    International Nuclear Information System (INIS)

    Silva, Danielle Cristina Tomaz da; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Campos, Dijon Henrique Salomé de; Nascimento, André Ferreira do; Oliveira, Sílvio Assis Junior de; Padovani, Carlos Roberto; Cicogna, Antonio Carlos

    2014-01-01

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C 15 and Ob 15 ) and 30 (C 30 and Ob 30 ) consecutive weeks. Obesity was determined by adiposity index. The Ob 15 group was similar to the C 15 group regarding the expression of myocardial collagen type I; however, expression in the Ob 30 group was less than C 30 group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob 30 when compared with Ob 15 . Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression

  7. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Danielle Cristina Tomaz da [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Lima-Leopoldo, Ana Paula; Leopoldo, André Soares [Departamento de Esportes, Centro de Educação Física e Desportos da Universidade Federal do Espírito Santo (UFES), Vitória, ES (Brazil); Campos, Dijon Henrique Salomé de; Nascimento, André Ferreira do [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Oliveira, Sílvio Assis Junior de [Escola de Fisioterapia da Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil); Padovani, Carlos Roberto [Departamento de Bioestatística do Instituto de Ciências Biológicas da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Cicogna, Antonio Carlos, E-mail: dany.tomaz@gmail.com [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-02-15

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C{sub 15} and Ob{sub 15}) and 30 (C{sub 30} and Ob{sub 30}) consecutive weeks. Obesity was determined by adiposity index. The Ob{sub 15} group was similar to the C{sub 15} group regarding the expression of myocardial collagen type I; however, expression in the Ob{sub 30} group was less than C{sub 30} group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob{sub 30} when compared with Ob{sub 15}. Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression.

  8. The compound Chinese medicine "Kang Fu Ling" protects against high power microwave-induced myocardial injury.

    Directory of Open Access Journals (Sweden)

    Xueyan Zhang

    Full Text Available BACKGROUND: The prevention and treatment of Microwave-caused cardiovascular injury remains elusive. This study investigated the cardiovascular protective effects of compound Chinese medicine "Kang Fu Ling" (KFL against high power microwave (HPM-induced myocardial injury and the role of the mitochondrial permeability transition pore (mPTP opening in KFL protection. METHODS: Male Wistar rats (100 were divided into 5 equal groups: no treatment, radiation only, or radiation followed by treatment with KFL at 0.75, 1.5, or 3 g/kg/day. Electrocardiography was used to Electrophysiological examination. Histological and ultrastructural changes in heart tissue and isolated mitochondria were observed by light microscope and electron microscopy. mPTP opening and mitochondrial membrane potential were detected by confocal laser scanning microscopy and fluorescence analysis. Connexin-43 (Cx-43 and endothelial nitric oxide synthase (eNOS were detected by immunohistochemistry. The expression of voltage-dependent anion channel (VDAC was detected by western blotting. RESULTS: At 7 days after radiation, rats without KFL treatment showed a significantly lower heart rate (P<0.01 than untreated controls and a J point shift. Myocyte swelling and rearrangement were evident. Mitochondria exhibited rupture, and decreased fluorescence intensity, suggesting opening of mPTP and a consequent reduction in mitochondrial membrane potential. After treatment with 1.5 g/kg/day KFL for 7 d, the heart rate increased significantly (P<0.01, and the J point shift was reduced flavorfully (P<0.05 compared to untreated, irradiated rats; myocytes and mitochondria were of normal morphology. The fluorescence intensities of dye-treated mitochondria were also increased, suggesting inhibition of mPTP opening and preservation of the mitochondrial membrane potential. The microwave-induced decrease of Cx-43 and VDAC protein expression was significantly reversed. CONCLUSION: Microwave radiation can

  9. [Case of law-evading herbs poisoning that induced shock and myocardial damage].

    Science.gov (United States)

    Nakamura, Yoshihiko; Nakano, Minoru; Nakamura, Mitsunobu; Miyazaki, Dai; Okamori, Satoshi; Akuzawa, Hisashi; Yuasa, Masahiro

    2014-12-01

    Law-evading herbs may induce poisoning symptoms, especially when they contain synthetic cannabinoids. However, their detailed pharmacological effects have not yet been clarified. Some reports have previously described symptoms of poisoning, but only a few reports have so far described shock and myocardial damage (MD). We experienced a case of shock and MD in a patient who had smoked law-evading herbs. A 61-year-old male presented at an emergency department 8 hours after smoking law-evading herbs (Rush Trip, High Men Monster) with chest pain. A vasopressor agent was administered to treat shock and antiarrhythmic drugs were administered due to ventricular arrhythmia. The contents of the law-evading herbs were unknown, so an in-hospital follow-up was conducted to treat the patient's symptoms. The follow-up blood test showed an increased level of cardiac enzymes, which thereafter demonstrated a spontaneous remission. The systemic conditions tended to improve and the patient was discharged from the hospital on the 5th hospital day. The contents of the law-evading herbs in question were thereafter,analyzed, and synthetic cannabinoids (JWH-210, JWH-081 and JWH-122) as well as caffeine were detected. The cause for the poisoning symptoms were suspected to be the presence of synthetic cannabinoids and caffeine. Such law-evading herbs may contain synthetic cannabinoids and caffeine which both may induce shock and MD.

  10. Improvement of pacing induced regional myocardial ischemia by Solcoseryl in conscious dogs with coronary stenosis.

    Science.gov (United States)

    Shimada, T; Sasayama, S; Takahashi, M; Osakada, G; Kawai, C

    1984-02-01

    The effects of Solcoseryl on regional myocardial function were studied in 5 conscious dogs with partial coronary constriction, in which temporary ischemia was induced by rapid cardiac pacing. During the coronary artery constriction, the percent shortening of the ischemic segment decreased by 9%. When the heart rate was increased by pacing, the percent shortening of the ischemic segments was further reduced by 57%. On cessation of cardiac pacing, the early potentiation of dP/dt and of control segment shortening became evident and was followed by exponential decay in the subsequent several beats. In the ischemic segment, the percent shortening was significantly improved in the first post-pacing beat but was more severely depressed at five seconds. Thirty minutes after administration of Solcoseryl, the cardiac pacing was repeated in the same manner but the pacing-induced hypokinesia of the ischemic segment were less marked, the percent shortening being at an average of 9.1% during control pacing and 12.7% during the second pacing after Solcoseryl (p less than 0.05). Postpacing deterioration of the ischemic segment shortening was also significantly improved from 9.8 to 11.8% at 5 seconds (p less than 0.05). These findings indicate that Solcoseryl exerts protective effects on the ischemic myocardium by promoting a rapid recovery from ischemia, probably due to the improvement of oxygen utility through activated cellular respiration.

  11. Raspberry ketone protects against isoproterenol-induced myocardial infarction in rats.

    Science.gov (United States)

    Khan, Vasim; Sharma, Sumit; Bhandari, Uma; Ali, Syed Mansoor; Haque, Syed Ehtaishamul

    2018-02-01

    The cardioprotective role of raspberry ketone (RK) against isoproterenol (ISO)-induced myocardial infarction (MI) in rats was assessed. Rats were randomly divided into Group I - Vehicle control; Group II - Toxic control ISO (85mg/kg, s.c.); Group III, IV and V - RK (50, 100 and 200mg/kg, respectively) with ISO; Group VI- RK (200mg/kg) alone; Group VII - Propranolol (10mg/kg) with ISO; and Group VIII - Propranolol (10mg/kg) alone. After twenty-four hours of the last dose, animals were sacrificed and creatine kinase-MB, lactate dehydrogenase, total cholesterol, triglycerides, high-density-lipoprotein, low-density-lipoprotein, very-low-density-lipoprotein, malondialdehyde, reduced glutathione, superoxide dismutase, catalase, Na + , K + -ATPase, nitric oxide, histopathological and immunohistochemical analysis (tumor necrosis factor-α and inducible nitric oxide synthase) were performed. Treatment with ISO significantly deviated the biochemical parameters from the normal levels, which were considerably restored by RK at 100 and 200mg/kg doses. 50mg/kg dose, however, did not demonstrate any significant cardioprotective action. The histopathological and immunohistochemical analysis further substantiated these findings. Our study showed a dose-dependent reduction in oxidative stress, inflammation and dyslipidemia by RK in ISO-intoxicated rats, which signifies that RK from the European red raspberry plant might be a valuable entity for the management of MI. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  13. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Drug-Induced Myocardial Infarction Secondary to Coronary Artery Spasm in Teenagers and Young Adults

    Directory of Open Access Journals (Sweden)

    Menyar Ayman

    2006-01-01

    Full Text Available There is no published registry for drug-induced acute myocardial infarction (AMI with subsequent patent coronary angiogram in teenagers. To highlight the mechanism and impact of drug-induced MI with patent coronary arteries among teenagers who have relatively few coronary risk factors in comparison with older patients, we conducted a review of the literature. In this review most of the pertinent published (English and non-English articles through the Medline, Scopus, Cochrane Database of Systematic Reviews, and EBSCO Host research databases from 1970 to 2005 have been revised. Teenagers and young adults with AMI and subsequent patent coronary angiogram were included. In those cases drug-induced coronary spasm was highlighted. Among 220 articles (>12000 cases related with AMI with normal coronary angiogram, 50 articles (~100 cases reported the role of drug in AMI secondary to coronary artery spasm (CAS. There is no well-conducted trial for AMI secondary to CAS in young adults but only a series of case reports, and the diagnosis in most of cases was based on the clinical and laboratory findings without provocation. CAS was associated with 12 illicit substances in teenagers (i.e., cocaine, marijuana, alcohol, butane, and amphetamine. Smoking is not only the initiative but also might harbor other illicit substances that increase the risk for CAS. Cocaine-associated AMI is the most frequent in various research papers. CAS was reported with 19 types of medications (i.e., over-the-counter, chemotherapy, antimigraine, and antibiotics without strong relation to age. Despite drug-induced AMI being not a common event, attention to smoking and drugs in teenagers and young adults will have major therapeutic and prognostic implications.

  15. Reactive Oxygen Species and Mitochondrial KATP Channels Mediate Helium-Induced Preconditioning Against Myocardial Infarction In Vivo

    Science.gov (United States)

    Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2008-01-01

    Objectives Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial KATP channels in this process are unknown. We tested the hypothesis that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=64) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial KATP antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of Student's t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (P<0.05) reduced infarct size (23±4% of the area at risk; mean±SD) compared with control (46±3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49±5, 45±6, and 45±3%), but these drugs blocked reductions in infarct size produced by helium (45±4, 45±2, and 44±3%). Conclusions The results suggest that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. PMID:18662630

  16. Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against ischemia-reperfusion injury-induced myocardial infarction

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    Manodeep Chakraborty

    2014-01-01

    Full Text Available Globally, the rate of development of myocardial diseases and hypertension is very common, which is responsible for incremental morbidity and mortality statistics. Treatment of ischemic hypertensive patients with diuretics such as hydrochlorothiazide (HCTZ can precipitate myocardial infarction due to hypokalemia. This study was undertaken to evaluate the pharmacodynamic interaction of green tea extract (GTE with HCTZ against ischemia-reperfusion induced myocardial toxicity. Wistar albino rats of either sex were taken and pretreated with high (500 mg/kg, p.o. and low (100 mg/kg, p.o. dose of GTE for 30 days. Standard, high and low dose of interactive groups received HCTZ (10 mg/kg, p.o. for last 7 days. Ischemia-reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, serum biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups, such as high and low dose of GTE and their interactive groups with HCTZ, exhibited significant percentage recovery in terms of heart rate and developed tension. Apart from that, significant increase in superoxide dismutase and catalase, decrease in thiobarbituric acid reactive species in heart tissue, as well as significant decrease in serum lactate dehydrogenase, creatinine phosphokinase-MB and N-acetylcysteine levels have also been documented. The present findings clearly suggest that GTE dose-dependently reduces myocardial toxicity due to ischemia, and combination with HCTZ can reduce the associated side-effects and exhibits myocardial protection.

  17. Scintigraphic myocardial imaging with sup(99m)Tc-labelled pyrophosphate of experimentally produced cardiomyopathy in dogs

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    Duska, F.; Novak, J.; Vizda, J.; Kubicek, J.; Kafka, P.; Mazurova, Y.; Bradna, P.

    1981-12-01

    Scintigraphic examination of the myocardium using sup(99m)Tc-labelled pyrophosphate was carried out in 10 dogs with experimentally produced cardiomyopathy. This was brought by introvenous administration of high doses of adrenalin and theophylline. The scan was positive in 8 out of 10 dogs. Hot foci were very extensive. The degree of accumulation was however low (2+). Histological examination of the myocardium using the light microscope showed only scarcely distinguishable damage to the tissue without the presence of necrosis. ECG examinations were normal in all cases. By means of sup(99m)Tc-labelled pyrophosphate even very small myocardial disorders can thus be detected. This fact may be of clinical importance for an early diagnosis of heart lesions.

  18. Myocardial Bridge

    Science.gov (United States)

    ... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge Article Info En español Your heart is made ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

  19. Myocardial motion and deformation patterns in an experimental swine model of acute LBBB/CRT and chronic infarct.

    Science.gov (United States)

    Duchateau, Nicolas; Sitges, Marta; Doltra, Adelina; Fernández-Armenta, Juan; Solanes, Nuria; Rigol, Montserrat; Gabrielli, Luigi; Silva, Etelvino; Barceló, Aina; Berruezo, Antonio; Mont, Lluís; Brugada, Josep; Bijnens, Bart

    2014-06-01

    In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: (pLBBBvsBaseline) < 0.001, (pCRTvsBaseline) = NS; non-corrected: (pLBBBvsBaseline) = NS, (pCRTvsBaseline) = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.

  20. Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.

    Science.gov (United States)

    Wendell, David C; Friehs, Ingeborg; Samyn, Margaret M; Harmann, Leanne M; LaDisa, John F

    2017-10-01

    Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Comparison of Hyperemic Impedance Echocardiography with Dobutamine Stress Echocardiography to Detect Inducible Myocardial Ischemia: A Pilot Study.

    Science.gov (United States)

    Patel, Jijibhoy J; Gupta, Ankur; Nanda, Navin C

    2016-03-01

    Stress echocardiography using exercise or pharmacological stressors is either contraindicated or associated with significant side effects in some patients. This pilot study was designed to evaluate a new technique, hyperemic impedance echocardiography (HIE). It is based on reactive coronary hyperemia when transient limb ischemia is induced by tourniquet inflation. We hypothesized that this physiologic coronary hyperemia can identify inducible myocardial ischemia by assessment of regional wall motion abnormalities on echocardiography when compared with dobutamine stress echocardiography (DSE). Twenty consecutive outpatients with suspected stable coronary artery disease (CAD) who underwent clinically indicated DSE were recruited for performance of HIE after informed consent was obtained. Standard graded dobutamine infusion protocol from 5 to 40 μg/kg per min was used for DSE. HIE was performed by inflating tourniquets at a pressure of 10 mmHg below the systolic blood pressure for 1 minute in three of four extremities at a time for total of four cycles. Echocardiography was performed immediately after the last rotating tourniquet deflation. DSE and HIE were classified as abnormal for development of new or worsening wall motion abnormality in at least one myocardial segment. Test characteristics were also determined for a subset of these patients (n = 12) who underwent clinically indicated coronary angiography. Hyperemic impedance echocardiography showed 86% sensitivity, 67% specificity, 86% positive predictive value, and 67% negative predictive value with a test accuracy of 80% to detect inducible myocardial wall motion abnormalities when compared with DSE. HIE also showed 83% sensitivity, 75% negative predictive value with a test accuracy of 66.7% for detection of significant (≥50% diameter stenosis) CAD on coronary angiography. In this pilot study, HIE was a feasible, safe, and promising method for detection of inducible myocardial ischemia by assessment of

  2. Mitochondrial DAMPs induce endotoxin tolerance in human monocytes: an observation in patients with myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Irene Fernández-Ruiz

    Full Text Available Monocyte exposure to mitochondrial Danger Associated Molecular Patterns (DAMPs, including mitochondrial DNA (mtDNA, induces a transient state in which these cells are refractory to further endotoxin stimulation. In this context, IRAK-M up-regulation and impaired p65 activity were observed. This phenomenon, termed endotoxin tolerance (ET, is characterized by decreased production of cytokines in response to the pro-inflammatory stimulus. We also show that monocytes isolated from patients with myocardial infarction (MI exhibited high levels of circulating mtDNA, which correlated with ET status. Moreover, a significant incidence of infection was observed in those patients with a strong tolerant phenotype. The present data extend our current understanding of the implications of endotoxin tolerance. Furthermore, our data suggest that the levels of mitochondrial antigens in plasma, such as plasma mtDNA, should be useful as a marker of increased risk of susceptibility to nosocomial infections in MI and in other pathologies involving tissue damage.

  3. Hypoglycaemia-induced myocardial infarction as a result of sulphonylurea misuse.

    LENUS (Irish Health Repository)

    Corley, B T

    2012-02-01

    BACKGROUND: Recent large-scale randomized trials of intensive therapy in Type 2 diabetes have reported increased cardiovascular morbidity and mortality in patient populations who experience a high frequency of hypoglycaemic events. However, there are few descriptions of hypoglycaemia leading directly to a myocardial infarction (MI) in the medical literature to date. CASE REPORT: In this article we describe the case of a 76-year-old woman without diabetes who presented with symptoms, left bundle branch block and raised troponin, indicative of an MI. She was also noted to be hypoglycaemic with a plasma glucose level of 2.5 mmol\\/l. It was subsequently discovered that she had mistakenly been dispensed glibenclamide, a long-acting sulphonylurea, in the preceding weeks. Her cardiac symptoms resolved completely upon treatment of her hypoglycaemia and she had no significant coronary artery disease on angiography. CONCLUSION: This is the first case of sulphonylurea-induced MI in a patient without diabetes and illustrates the adverse effects of acute hypoglycaemia upon the cardiovascular system.

  4. NF-κB-mediated inflammation correlates with calcium overload under arsenic trioxide-induced myocardial damage in Gallus gallus.

    Science.gov (United States)

    Li, Siwen; Wang, Yu; Zhao, Hongjing; He, Ying; Li, Jinglun; Jiang, Guangshun; Xing, Mingwei

    2017-10-01

    Arsenic is a known environmental pollutant and highly hazardous toxin to human health. Due to the biological accumulation, arsenic produces a variety of cardiovascular diseases. However, the exact mechanism is still unclear. Here, our objective was to evaluate myocardial damage and determine the potential mechanism under arsenic exposure in chickens. Arsenic trioxide (As 2 O 3 ) (1.25 mg/kg BW, corresponding 15 mg/kg feed) was administered as basal diet to male Hy-line chickens (one-day-old) for 4, 8 and 12 weeks. The results showed that As 2 O 3 -induced histological and ultrastructural damage in heart accompanied with significantly Ca 2+ overload and increased the activities of myocardial enzymes. Moreover, As 2 O 3 exposure significantly increased (P CACNA1S and interleukin-10 were decreased (P < 0.05) by As 2 O 3 exposure at 4, 8 and 12 weeks as compared with the corresponding control group. Western blot results showed that As 2 O 3 exposure decreased the expression of SERCA and SLC8A1 protein, while the expression of TNF-α, NF-κB, iNOS and PMCA1 increased compared with the corresponding control group. Additionally, correlation analysis and protein-protein interaction prediction shown that NF-κB-mediated inflammatory response have a function correlation with calcium (Ca) regulation-related genes. In conclusion, this study indicated that As 2 O 3 -induced inflammatory response might dependent on Ca overload in myocardial damage of chickens. Our work has implications for the development of potential therapeutic approaches by resisting Ca overload for arsenic-induced myocardial damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Inflammation in lung after acute myocardial infarction is induced by dendritic cell-mediated immune response.

    Science.gov (United States)

    Hu, L J; Ren, W Y; Shen, Q J; Ji, H Y; Zhu, L

    2017-01-01

    The present study was performed to describe the changes of lung tissues in mice with acute myocardial infarction (AMI) and also explain the cell mechanism involved in inflammation in lung. AMI was established by left coronary ligation in mice. Then mice were divided into three groups: control group, MW1 group (sampling after surgery for one week) and MW2 group (sampling after surgery for two weeks). Afterwards, measurement of lung weight and lung histology, cell sorting in bronchoalveolar lavage (BAL) fluid and detection of several adhesive molecules, inflammatory molecules as well as enzyme associated with inflammation were performed. Moreover, dendritic cells (DCs) were isolated from bone marrow of C57B/L6 mice. After incubating with necrotic myocardium, the expression of antigen presenting molecules, co-stimulatory molecules and inflammatory molecules were detected by flow cytometry or immunohistochemistry in DCs. We also detected T-cell proliferation after incubating with necrotic myocardium-treated DCs. AMI induced pathological changes of lung tissue and increased inflammatory cell amount in BAL fluid. AMI also increased the expression of several inflammatory factors, adhesive molecules and enzymes associated with inflammation. CD11c and TLR9, which are DC surface markers, showed a significantly increased expression in mice with AMI. Additionally, necrotic myocardium significantly increased the expression of co-stimulatory factors including CD83 and CD80, inflammatory cytokines including TNF-α, IFN-γ and NF-κB in DCs. Furthermore, DCs treated with necrotic myocardium also significantly promoted T-cell proliferation. AMI induced inflammation in lung and these pathological changes were mediated by DC-associated immune response.

  6. Technetium-99m isonitrile complex as a potential myocardial imaging agent

    International Nuclear Information System (INIS)

    Khalil, M.N.; Hubner, P.J.B.; Thornback, J.; Early, M.Y; Berry, J.M.; Morton, D.B.

    1985-01-01

    99 Tcsup(m)-tertiary butyl isonitrile (BIN) was assessed as a myocardial imaging agent in 4 dogs with normal hearts and three with experimentally induced myocardial infarction. Results are presented showing normal cardiac images, the detection of antero-apical infarcts, plasma clearance curves and tissue distribution in various organs. It is suggested that 99 Tcsup(m)-BIN has a potential role as a myocardial imaging agent in man. (U.K.)

  7. Glycogen phosphorylase isoenzyme BB plasma kinetics is not related to myocardial ischemia induced by exercise stress echo test.

    Science.gov (United States)

    Dobric, Milan; Giga, Vojislav; Beleslin, Branko; Ignjatovic, Svetlana; Paunovic, Ivana; Stepanovic, Jelena; Djordjevic-Dikic, Ana; Kostic, Jelena; Nedeljkovic, Ivana; Nedeljkovic, Milan; Tesic, Milorad; Dajak, Marijana; Ostojic, Miodrag

    2013-10-01

    Glycogen phosphorylase BB (GPBB) is released from cardiac cells during myocyte damage. Previous studies have shown contradictory results regarding the relation of enzyme release and reversible myocardial ischemia. The aim of this study was to determine the plasma kinetics of GPBB as a response to the exercise stress echocardiographic test (ESET), and to define the relationship between myocardial ischemia and enzyme plasma concentrations. We studied 46 consecutive patients undergoing ESET, with recent coronary angiography. In all patients, a submaximal stress echo test according to Bruce protocol was performed. Concentration of GPBB was measured in peripheral blood that was sampled 5 min before and 10, 30 and 60 min after ESET. There was significant increase of GPBB concentration after the test (p=0.021). Significant increase was detected 30 min (34.9% increase, p=0.021) and 60 min (34.5% increase, p=0.016) after ESET. There was no significant effect of myocardial ischemia on GPBB concentrations (p=0.126), and no significant interaction between sampling intervals and myocardial ischemia, suggesting a similar release profile of GPBB in ischemic and non-ischemic conditions (p=0.558). Patients in whom ESET was terminated later (stages 4 or 5 of standard Bruce protocol; n=13) had higher GPBB concentrations than patients who terminated ESET earlier (stages 1, 2 or 3; n=33) (p=0.049). Baseline GPBB concentration was not correlated to any of the patients' demographic, clinical and hemodynamic characteristics. GPBB plasma concentration increases after ESET, and it is not related to inducible myocardial ischemia. However, it seems that GPBB release during ESET might be related to exercise load/duration.

  8. 99mTc-annexin V and 111In-antimyosin antibody uptake in experimental myocardial infarction in rats

    International Nuclear Information System (INIS)

    Sarda-Mantel, Laure; Rouzet, Francois; Martet, Genevieve; Raguin, Olivier; Vrigneaud, Jean-Marc; Guludec, Dominique Le; Michel, Jean-Baptiste; Louedec, Liliane; Vanderheyden, Jean-Luc; Hervatin, Florence; Khaw, Ban An

    2006-01-01

    99m Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ( 111 In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain). The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats. All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1±0.6 versus 1.5±0.3 (p=0.001) for ANX and 1.99±0.44 versus 1.01±0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6±0.9 versus 5.0±1.8 at 24 h), while Apostain staining was very low (0.06±0.06% of cells). In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas. (orig.)

  9. The study with 13N-NH3 PET and coronary angiography to investigate the effect of CD151 gene therapy on swines with experimental myocardial infarction

    International Nuclear Information System (INIS)

    Zuo Houjuan; Liu Zhengxiang; Liu Xiaochun; Ceng Hesong; Liu Tao; Wen Sha; Chen Jin; Wang Daowen

    2009-01-01

    Objective: Our previous studies showed that CD151 could promote neovascularization in a rat hind-limb ischemia model and in a rat myocardial ischemia model. This study was to determine the change of myocardial perfusion and coronary collateralization after intramyocardial administration CD151 in swines with experimental myocardial infarction. Methods: CD151 and antiCD151 were constructed into the recombinant adeno-associated virus vector (rAAV). Twenty swines received coronary artery ligation and intramuscular injection of rAAV-CD151 or rAAV-green fluorescent protein (GFP). Eight weeks after vector administration, the expression of CD151 protein and the capillary density were measured using immunohistochemistry. Regional myocardial perfusian was evaluated by 13 N-NH 3 PET. Coronary angiography was per-formed to assess collateral vessels reconstruction. The t-test or ANOVA with SPSS 11.0 was used for data analysis. Results: High levels of CD151 protein expression and capillary density were detected in the rAAV-CD151 group. 13 N-NH 3 PET imaging showed that myocardial perfusion was improved and the myocardial ischemia scores were significantly decreased in the rAAV-CD151 group when compared with rAAV-GFP group (10.82 ± 2.36 vs 19.33 ± 1.67, t=5.86, P=0.002).Coronary angiography confirmed better collateral circulation in the rAAV-CD151 group. Conclusions: rAAV-CD151 direct injection can transfect the myocardium and express the CD151 protein, thereby significantly improve the myocardial blood perfusion and coronary collateralization. 13 N-NH 3 PET and coronary angiography can be used directly to evaluate the col-lateral vessel reconstruction and perfusion status of swine myocardium. (authors)

  10. The role of chemokine ligand 16 in high salt induced myocardial remodeling in salt sensitive hypertensive rats

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    Mei-li LIU

    2015-11-01

    Full Text Available Objective To investigate the effects of chemokine ligand 16 (CXCL16 in high salt induced myocardial remodeling in salt sensitive hypertensive rats. Methods Sixty-four Dahl salt sensitive (Dahl-SS rats were randomly divided into normal salt (NS, 0.3% NaCl and high salt (HS, 8.0% NaCl group, 32 rats for each group. Blood pressure was measured by tail-cuff method every week. Hearts were harvested and the expression of CXCL16 in heart tissues was detected by Western blotting at the 2nd, 4th, 6th and 8th week after NS or HS feeding. Immunofluorescence double staining was used to detect the colocalization of CXCL16 with both cardiomyocytes and cardiac fibroblasts. Immunofluorescence and immunohistochemical staining were used to detect the expression of CXCL16 and the biomarker of macrophage in the myocardial tissue after 6 week and 8 week of NS or HS feeding. Myocardial fibrosis was evaluated by HE and Masson trichrome staining. Results Compared with that in NS group, the systolic pressure and diastolic pressure in HS group increased significantly after 1 week of HS feeding (147.10±3.67mmHg vs128.57±6.32mmHg, P<0.01 and 110.86±4.24mmHg vs90.69±4.51mmHg, P<0.01, respectively. HS feeding significantly increased the myocardial CXCL16 expression in rats of HS group at the 6th week (1.18±0.05 vs0.58±0.02, P<0.05, and the expression of CXCL16 was further up-regulated at the 8th week (1.43±0.06 vs0.67±0.03, P<0.05. At the 8th week, obvious fibrosis remodeling and macrophage infiltration appeared in the myocardial tissue of the rats in HS group. Conclusion High salt intervention could up-regulate the expression of CXCL16 in salt sensitive hypertensive myocardial remodeling, which may promote macrophage infiltration and participate in the pathological process of myocardial fibrosis accordingly. DOI: 10.11855/j.issn.0577-7402.2015.11.04

  11. Myocardial Ischemia Induces SDF-1α Release in Cardiac Surgery Patients.

    Science.gov (United States)

    Kim, Bong-Sung; Jacobs, Denise; Emontzpohl, Christoph; Goetzenich, Andreas; Soppert, Josefin; Jarchow, Mareike; Schindler, Lisa; Averdunk, Luisa; Kraemer, Sandra; Marx, Gernot; Bernhagen, Jürgen; Pallua, Norbert; Schlemmer, Heinz-Peter; Simons, David; Stoppe, Christian

    2016-06-01

    In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

  12. Microarray Expression Profile of Circular RNAs in Heart Tissue of Mice with Myocardial Infarction-Induced Heart Failure

    Directory of Open Access Journals (Sweden)

    Hong-Jin Wu

    2016-06-01

    Full Text Available Background/Aims: Myocardial infarction (MI is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. This study is aimed to assess the global changes in and characteristics of the transcriptome of circular RNAs (circRNAs in heart tissue during MI induced heart failure (HF. Methods: Using a post-myocardial infarction (MI model of HF in mice, we applied microarray assay to examine the transcriptome of circRNAs deregulated in the heart during HF. We confirmed the changes in circRNAs by quantitative PCR. Results: We revealed and confirmed a number of circRNAs that were deregulated during HF, which suggests a potential role of circRNAs in HF. Conclusions: The distinct expression patterns of circulatory circRNAs during HF indicate that circRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.

  13. Effect of Escitalopram on Mental Stress-Induced Myocardial Ischemia: The Results of the REMIT Trial

    Science.gov (United States)

    Jiang, Wei; Velazquez, Eric J.; Kuchibhatla, Maragatha; Samad, Zainab; Boyle, Stephen H.; Kuhn, Cynthia; Becker, Richard C.; Ortel, Thomas L.; Williams, Redford B.; Rogers, Joseph G.; O’Connor, Christopher

    2015-01-01

    Importance Mental-stress-induced myocardial ischemia (MSIMI) is an intermediate surrogate endpoint representing the pathophysiological link between psychosocial risk factors and adverse outcomes of coronary heart disease (CHD). However, pharmacological interventions aimed at reducing MSIMI have not been well studied. Objective To examine the effects of 6 weeks of escitalopram treatment vs. placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. Design, Setting, and Participants The REMIT study is a randomized, double-blind, placebo-controlled trial of patients with clinically stable CHD and laboratory MSIMI. Enrollment occurred from 7/24/2007–8/24/2011 at a tertiary medical center. Interventions Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg with titration to 20 mg/day in 3 weeks) or placebo over 6 weeks. Main Outcome Measure Occurrence of MSIMI, defined as (1) development or worsening of regional wall motion abnormality; (2) left ventricular ejection fraction reduction ≥8%; and/or (3) horizontal or downsloping ST-segment depression ≥1mm in ≥2 leads lasting for ≥3 consecutive beats during ≥1 of 3 mental tasks. Results 127 participants were randomized to escitalopram (n=64) or placebo (n=63); 112 (96.1%) completed endpoint assessments (n=56 in each arm). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4 to 43.0]) had absence of MSIMI during the 3 mental stressors compared with patients taking placebo (17.5% [95% CI, 10.4 to 24.5]) based on unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (OR=2.62 [95% CI, 1.06 to 6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6 to 55.0]) than in patients receiving placebo (52.5% [95% CI, 43.3 to 61.7]), compared with baseline escitalopram (49.2% [95% CI, 39.9 to

  14. High Concordance Between Mental Stress-Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and Biomarker Correlates.

    Science.gov (United States)

    Wawrzyniak, Andrew J; Dilsizian, Vasken; Krantz, David S; Harris, Kristie M; Smith, Mark F; Shankovich, Anthony; Whittaker, Kerry S; Rodriguez, Gabriel A; Gottdiener, John; Li, Shuying; Kop, Willem; Gottlieb, Stephen S

    2015-10-01

    Mental stress can trigger myocardial ischemia, but the prevalence of mental stress-induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress-induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion. Thirty-four coronary artery disease patients (mean age±SD, 62±10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model. Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179±65 mL at rest and increased to 217±71 after mental stress and 229±86 after adenosine (Pmental stress (Pmental stress. Ejection fraction was 30±12 at baseline, 29±11 with mental stress, and 28±10 with adenosine (P=not significant). There was high concordance between ischemic perfusion defects induced by adenosine and mental stress, suggesting that mental stress is equivalent to pharmacologic stress in eliciting clinically significant myocardial perfusion defects in CHF patients. Cardiac dilatation suggests clinically important changes with both

  15. Further insights into blood pressure induced premature beats: Transient depolarizations are associated with fast myocardial deformation upon pressure decline.

    Science.gov (United States)

    Haemers, Peter; Sutherland, George; Cikes, Maja; Jakus, Nina; Holemans, Patricia; Sipido, Karin R; Willems, Rik; Claus, Piet

    2015-11-01

    An acute increase in blood pressure is associated with the occurrence of premature ventricular complexes (PVCs). We aimed to study the timing of these PVCs with respect to afterload-induced changes in myocardial deformation in a controlled, preclinically relevant, novel closed-chest pig model. An acute left ventricular (LV) afterload challenge was induced by partial balloon inflation in the descending aorta, lasting 5-10 heartbeats (8 pigs; 396 inflations). Balloon inflation enhanced the reflected wave (augmentation index 30% ± 8% vs 59% ± 6%; P blood pressure by 35% ± 4%. This challenge resulted in a more abrupt LV pressure decline, which was delayed beyond ventricular repolarization (rate of pressure decline 0.16 ± 0.01 mm Hg/s vs 0.27 ± 0.04 mm Hg/ms; P pressure 1 ± 12 ms vs 36 ± 9 ms; P = .008), during which the velocity of myocardial shortening at the basal septum increased abruptly (ie, postsystolic shortening) (peak strain rate -0.6 ± 0.5 s(-1) vs -2.5 ± 0.8 s(-1); P pressure decline, with increased postsystolic shortening, and not at peak pressure, that PVCs occur (22% of inflations). These PVCs preferentially occurred at the basal and apical segments. In the same regions, monophasic action potentials demonstrated the appearance of delayed afterdepolarization-like transient depolarizations as origin of PVCs. An acute blood pressure increase results in a more abrupt LV pressure decline, which is delayed after ventricular repolarization. This has a profound effect on myocardial mechanics with enhanced postsystolic shortening. Coincidence with induced transient depolarizations and PVCs provides support for the mechanoelectrical origin of pressure-induced premature beats. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  16. Infarto do miocárdio induzido por cocaína Cocaine-induced myocardial infarction

    Directory of Open Access Journals (Sweden)

    Henrique Pott Junior

    2009-10-01

    Full Text Available Com os aumentos da difusão e da facilidade de acesso à cocaína, registra-se aumento da morbidade e da mortalidade associadas ao seu uso. O seu consumo tem sido associado a doenças cardiovasculares (DCVs, entre elas isquemia e infarto do miocárdio. Desde o primeiro relato de associação entre o consumo de cocaína, isquemia miocárdica e infarto, os efeitos cardiovasculares da cocaína vêm sendo amplamente estudados, a fim de se estabelecerem seus mecanismos fisiopatológicos, alterações estruturais, diagnóstico, repercussões hemodinâmicas e prognóstico. O objetivo deste estudo foi relatar um caso de múltiplos infartos do miocárdio induzido pelo uso de cocaína com estudo necroscópico.The increased distribution and access to cocaine, lead to an increase of morbidity and mortality associated with its use. Cocaine use has been associated with cardiovascular diseases, among them ischemia and myocardial infarction. Since the first report of association between the use of cocaine, myocardial ischemia and infarction in 1982, the cardiovascular effects of cocaine have been extensively studied in order to establish its pathophysiological mechanism, structural changes, methods of diagnosis, prognosis and homodynamic effects. This study reports a case of multiple myocardial infarction induced by the use of cocaine with necroscopic study.

  17. Mouse Sirt3 promotes autophagy in AngII-induced myocardial hypertrophy through the deacetylation of FoxO1.

    Science.gov (United States)

    Li, Jingyuan; Chen, Tongshuai; Xiao, Ming; Li, Na; Wang, Shujian; Su, Hongyan; Guo, Xiaobin; Liu, Hui; Yan, Fangying; Yang, Yi; Zhang, Yun; Bu, Peili

    2016-12-27

    Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member proven to promote longevity in mammalian Sirtuin family. The processed short form of Sirt3 has been demonstrated to target many mediators of energy metabolism and mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling mechanism and provides energy or metabolic substrates. Among the mechanisms triggered by cardiac stress, opinions vary as to whether autophagy is a protective or detrimental response. Here, by inducing the Sirt3-knockout mice to myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we determined the role of Sirt3 in myocardial hypertrophy and autophagy. In this study, the Sirt3-knockout mice developed deteriorated cardiac function and impaired autophagy compared to wild-type mice. What's more, the overexpression of Sirt3 by lentivirus transfection attenuated cardiomyocytes hypertrophy by promoting autophagy. We further demonstrated that Sirt3 could bind to FoxO1 and activate its deacetylation. Sequentially, deacetylated FoxO1 translocates to the nucleus where it facilitates downstream E3 ubiquitin ligases such as Muscle RING Finger 1 (MuRF1) and muscle atrophy F-box (MAFbx, Atrogin1). Altogether, these results revealed that Sirt3 activation is essential to improve autophagy flux by reducing the acetylation modification on FoxO1, which in turn alleviates myocardial hypertrophy.

  18. Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Xiao J

    2016-03-01

    Full Text Available Jie Xiao, Xi Sheng, Xinyu Zhang, Mengqi Guo, Xiaoping JiKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaAbstract: Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1 in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart.Keywords: curcumin, myocardial infarction, angiotensin II, cardiac fibroblasts, fibrosis, SIRT1

  19. Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Andre Chow

    2017-11-01

    Full Text Available Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG, human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM, and erythropoietin (EPO therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment.

  20. Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

    International Nuclear Information System (INIS)

    Gharanei, M.; Hussain, A.; Janneh, O.; Maddock, H.L.

    2013-01-01

    Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

  1. Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

    Energy Technology Data Exchange (ETDEWEB)

    Gharanei, M.; Hussain, A. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Janneh, O. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Pharmacology Research Laboratories, 70, Pembroke Place, The University of Liverpool, Liverpool. L69 3GF (United Kingdom); Maddock, H.L., E-mail: h.maddock@coventry.ac.uk [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom)

    2013-04-15

    Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

  2. Acute myocardial infarction induced by concurrent use of adderall and alcohol in an adolescent.

    Science.gov (United States)

    Sharma, Jayendra; de Castro, Carlyle; Chatterjee, Partha; Pinto, Rohit

    2013-01-01

    Adderall (amphetamine, dextroamphetamine mixed salts), a widely prescribed stimulant for the treatment of attention-deficit/hyperactivity disorder in children and adolescents, is considered safe with due precautions. Nonmedical use of Adderall is prevalent and rising in high school and college students. Use of prescribed Adderall without intention to overdose as a cause of myocardial infarction is extremely rare, and to our knowledge, only 3 cases have been reported in the pediatric literature. We report a case of acute myocardial infarction in an adolescent without cardiovascular risk factors who took the total prescribed daily dose of Adderall one time while consuming alcohol. The sporadic use of Adderall with alcohol creates a potentially dangerous situation with serious cardiovascular adverse effects. We should have a high degree of suspicion for children and adolescents on stimulant therapy who present with chest pain and an abnormal electrocardiogram in the pediatric emergency department, and there is a need to evaluate them for myocardial ischemia and infarction.

  3. Significance of exercise-induced ST segment depression in patients with myocardial infarction involving the left circumflex artery. Evaluation by exercise thallium-201 myocardial single photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Koitabashi, Norimichi; Toyama, Takuji; Hoshizaki, Hiroshi [Gunma Prefectural Cardiovascular Center, Maebashi (Japan)] [and others

    2000-04-01

    The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography (Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement (angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V{sub 2}, V{sub 3} and V{sub 4} leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aV{sub F}, V{sub 5} and V{sub 6} leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression (p<0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium. (author)

  4. Significance of exercise-induced ST segment depression in patients with myocardial infarction involving the left circumflex artery. Evaluation by exercise thallium-201 myocardial single photon emission computed tomography

    International Nuclear Information System (INIS)

    Koitabashi, Norimichi; Toyama, Takuji; Hoshizaki, Hiroshi

    2000-01-01

    The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography (Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement (angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V 2 , V 3 and V 4 leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aV F , V 5 and V 6 leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression (p<0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium. (author)

  5. Intra- and interpersonal consequences of experimentally induced concealment

    NARCIS (Netherlands)

    Bouman, T.K.

    2003-01-01

    Secrecy, concealment, and thought supression are assumed to be important aspects of psychopathology. However, most studies address these from an intrapersonal perspective. This study investigates both the intra- as well as the interpersonal consequences of experimentally induced concealment. Two

  6. The Compound Chinese Medicine “Kang Fu Ling” Protects against High Power Microwave-Induced Myocardial Injury

    Science.gov (United States)

    Zhang, Xueyan; Gao, Yabing; Dong, Ji; Wang, Shuiming; Yao, Binwei; Zhang, Jing; Hu, Shaohua; Xu, Xinping; Zuo, Hongyan; Wang, Lifeng; Zhou, Hongmei; Zhao, Li; Peng, Ruiyun

    2014-01-01

    Background The prevention and treatment of Microwave-caused cardiovascular injury remains elusive. This study investigated the cardiovascular protective effects of compound Chinese medicine “Kang Fu Ling” (KFL) against high power microwave (HPM)-induced myocardial injury and the role of the mitochondrial permeability transition pore (mPTP) opening in KFL protection. Methods Male Wistar rats (100) were divided into 5 equal groups: no treatment, radiation only, or radiation followed by treatment with KFL at 0.75, 1.5, or 3 g/kg/day. Electrocardiography was used to Electrophysiological examination. Histological and ultrastructural changes in heart tissue and isolated mitochondria were observed by light microscope and electron microscopy. mPTP opening and mitochondrial membrane potential were detected by confocal laser scanning microscopy and fluorescence analysis. Connexin-43 (Cx-43) and endothelial nitric oxide synthase (eNOS) were detected by immunohistochemistry. The expression of voltage-dependent anion channel (VDAC) was detected by western blotting. Results At 7 days after radiation, rats without KFL treatment showed a significantly lower heart rate (Pmicrowave-induced decrease of Cx-43 and VDAC protein expression was significantly reversed. Conclusion Microwave radiation can cause electrophysiological, histological and ultrastructural changes in the heart. KFL at 1.5 g/kg/day had the greatest protective effect on these cardiovascular events. mPTP plays an important role in the protective effects of KFL against microwave-radiation-induced myocardial injury. PMID:24992449

  7. Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

    Science.gov (United States)

    da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

    2015-10-01

    The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

  8. Status of experimental data for neutron induced reactions

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Mamoru [Tohoku Univ., Sendai (Japan)

    1998-11-01

    A short review is presented on the status of experimental data for neutron induced reactions above 20 MeV based on the EXFOR data base and journals. Experimental data which were obtained in a systematic manner and/or by plural authors are surveyed and tabulated for the nuclear data evaluation and the benchmark test of the evaluated data. (author). 61 refs.

  9. The role of oxidative stress and lipid peroxidation in ventricular remodeling induced by tobacco smoke exposure after myocardial infarction.

    Science.gov (United States)

    Duarte, Daniella R; Minicucci, Marcos F; Azevedo, Paula S; Matsubara, Beatriz B; Matsubara, Luiz S; Novelli, Ethel L; Paiva, Sergio A R; Zornoff, Leonardo A M

    2009-01-01

    To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction. After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses. Rats in the ETS group showed higher diastolic (C = 1.52 +/- 0.4 mm(2), ETS = 1.95 +/- 0.4 mm(2); p=0.032) and systolic (C = 1.03 +/- 0.3, ETS = 1.36 +/- 0.4 mm(2)/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 +/- 10.1 %, ETS = 19.2 +/- 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 +/- 2.2, ETS = 5.1 +/- 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3-4.8), ETS = 5.5 (5.3-5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 +/- 7.6 nmol/mg of protein, ETS = 40.7 +/- 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 +/- 0.1 nmol/g of protein, ETS = 0.9 +/- 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 +/- 0.2 nmol/mg of tissue, ETS = 0.1 +/- 0.1 nmol/mg of tissue; p=0.08). In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular remodeling after myocardial infarction.

  10. Characteristic findings of exercise ECG test, perfusion SPECT and coronary angiography in patients with exercise induced myocardial stunning

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol; Seo, Ji Hyoung; Bae, Jin Ho; Jeong, Shin Young; Park, Hun Sik; Lee, Jae Tae; Chae, Shung Chull; Lee, Kyu Bo [School of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-06-01

    Transient wall motion abnormality and contractile dysfunction of the left ventricle (LV) can be observed in patients with coronary artery disease due to post-stress myocardial stunning. To understand clinical characteristics of stress induced LV dysfunction, we have compared the findings of exercise stress test, myocardial perfusion SPECT and coronary angiography between subjects with and without post-stress LV dysfunction. Among subjects who underwent exercise stress test, myocardial perfusion SPECT and coronary angiography within a month of interval, we enrolled 36 patients with post-stress LV ejection fraction (LVEF) was {>=}5% lower than rest (stunning group) and 16 patients with difference of post-stress and rest LVEF was lesser than 1% (non-stunning group) for this study. Treadmill exercise stress gated myocardial perfusion SPECT was performed with dual head SPECT camera using 740 MBq Tc-99m MIBI and coronary angiography was also performed by conventional Judkins method. Stunning group had a significantly higher incidence of hypercholesterolemia than non-stunning group(45.5 vs 7.1%, p=0.01). Stunning group also had higher incidence of diabetes mellitus and lower incidence of hypertension, but these were not statistically significant. Stunning group had larger and more severe perfusion defect in stress perfusion myocardial SPECT than non-stunning group(extent 18.2 vs 9.2%, p=0.029; severity 13.5 vs 6.9, p=0.040). Stunning group also had higher degree of reversibility of perfusion defect, higher incidence of positive exercise stress test and higher incidence of having severe stenosis(80{approx}99%) in coronary angiography than non-stunning group, but these were not statistically significant. In stunning group, all of 4 patients without perfusion defect had significant coronary artery stenosis and had received revascularization treatment. Patients with post-stress LV dysfunction had larger and more severe perfusion defect and severe coronary artery stenosis than

  11. Myocardial metabolism of 123I-BMIPP during low-flow ischaemia in an experimental model: comparison with myocardial blood flow and 18F-FDG

    International Nuclear Information System (INIS)

    Hosokawa, Ryohei; Nohara, Ryuji; Hirai, Taku; Fujita, Masatoshi; Sasayama, Shigetake; Fujibayashi, Yasuhisa; Magata, Yasuhiro; Tadamura, Eiji; Konishi, Junji

    2001-01-01

    Risk stratification of coronary artery disease may provide a basis for selection of treatment to prevent myocardial events and to assist functional recovery. Iodine-123 (ρ-iodophenyl)-3-R,S-methylpentadecanoic acid ( 123 I-BMIPP) is a radioiodinated fatty acid analogue for single-photon emission tomographic (SPET) imaging, and several reports have demonstrated that the abnormal uptake of 123 I-BMIPP is associated with wall motion abnormality and severe coronary artery stenosis. Clarification of the contribution of fatty acids to myocardial metabolism would be highly valuable in recognising this critical condition. In this study, we investigated the myocardial uptake of 123 I-BMIPP under low-flow ischaemia, and compared it with the uptake of fluorine-18 fluorodeoxyglucose ( 18 F-FDG). Using open chest dogs, the flow of the left anterior descending coronary artery was controlled using a pneumatic occluder in order to maintain a 30%-40% reduction of Doppler flow. 123 I-BMIPP and 18 F-FDG were injected into the left atrium after 90 min of ischaemia (protocols 1 and 3). Canine hearts were excised after 120 min of ischaemia for the measurement of radioactivity. In protocol 2, 123 I-BMIPP alone was injected and hearts were excised 8 min after the injection. A time-course biopsy study was also performed at the same time (protocol 3). Wall thickening was evaluated using a wall tracker module. The uptake of 18 F-FDG increased significantly in the ischaemic region (232%±135% vs non-ischaemic, P 18 F-FDG did not correlate well with the severity of MBF. On the other hand, 123 I-BMIPP uptake decreased gradually (78.9%±23.6%, P 123 I-BMIPP was associated not only with wall motion abnormality but also with the severity of MBF. In the biopsy study (protocol 3), the radioactivity of either 123 I-BMIPP or 18 F-FDG correlated well with the MBF at the time of tracer injection and was similar to post-mortem analysis. It is concluded that 18 F-FDG is a valid tool for identifying

  12. Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure.

    Science.gov (United States)

    Merabet, Nassiba; Bellien, Jeremy; Glevarec, Etienne; Nicol, Lionel; Lucas, Daniele; Remy-Jouet, Isabelle; Bounoure, Frederic; Dreano, Yvonne; Wecker, Didier; Thuillez, Christian; Mulder, Paul

    2012-03-01

    The study addressed the hypothesis that soluble epoxide hydrolase (sEH) inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids (EETs), exerts beneficial effects in an established chronic heart failure (CHF) model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after coronary ligation) and delayed 3-day (starting 47 days after coronary ligation) treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 42-day AUDA increased plasma EETs demonstrating the effective inhibition of sEH. Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial pressure, thus reducing total peripheral resistance. Both treatment periods increased the slope of the LV end-systolic pressure-volume relation, but only 42-day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the slope of the LV end-diastolic pressure-volume relation, associated with a reduced LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent, 42-day AUDA increased LV perfusion associated with a decreased LV hypoxia-inducible factor-1alpha. Both treatment periods decreased reactive oxygen species level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, an inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished the beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation of EET availability by pharmacological inhibition of sEH increases LV diastolic and systolic functions in established CHF. This notably results from short-term processes, i.e. increased LV perfusion, reduced LV oxidative stress and peripheral vasodilatation, but also from long-term effects, i.e. reduced LV remodeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

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

  14. Experimental induced avian E. coli salpingitis

    DEFF Research Database (Denmark)

    Olsen, Rikke Heidemann; Thøfner, Ida; Pors, Susanne Elisabeth

    2016-01-01

    Several types of Escherichia coli have been associated with extra-intestinal infections in poultry, however, they may vary significantly in their virulence potential. The aim of the present study was to investigate the virulence of five strains of E. coli obtained from different disease manifesta......Several types of Escherichia coli have been associated with extra-intestinal infections in poultry, however, they may vary significantly in their virulence potential. The aim of the present study was to investigate the virulence of five strains of E. coli obtained from different disease...... manifestations or from the cloacae of a healthy chicken. The virulence potential of the strains were evaluated in an avian experimental model for ascending infections, and experiments were conducted in both layers and broiler breeders. The clinical outcome of infection was highly depending on the challenge......) had a distinct ability to cause disease. Results of the study shows major differences in virulence of different strains of E. coli in ascending infections; however, there was no indication of tissue-specific adaptation, since strains obtained from lesions unrelated to the reproductive system were...

  15. Experimental neuromyopathy induced by thallium in rats.

    Science.gov (United States)

    Barroso-Moguel, R; Mendez-Armenta, M; Villeda-Hernandez, J; Rios, C; Galvan-Arzate, S

    1996-01-01

    A histopathological study, with a light microscope, of experimental neuromyopathy produced by thallotoxicosis was undertaken in 40 newborn Wistar rats. Treatment consisted of a single i.p. injection of an aqueous solution of 16 mg kg-1 thallium(I) acetate 1 day after birth. Groups of ten animals were euthanized at either 8 or 50 days of age. Sural nerves, as well as peroneus muscle, were fixed in 10% formaldehyde solution for 15 days and then prepared for histopathological observation. At 8 days of age sural nerves of thallium-treated animals showed a moderate reduction in the large- and medium-sized fibres and several of the myelin sheaths had initial degeneration along the course of the axon. Interstitial oedema was found in both neural and muscular tissues. Distinct features of focal necrosis as well as small haemorrhages were seen in peroneus muscle. At 50 days of age, the lesions were more diffuse. Large and small myelinated fibres were found to be sinuous, fragmented and scanty. Alterations in the large- and medium-sized axons were seen and the myelin sheaths were altered along the course of the axon, suggesting a progressive distal axonopathy. Additionally, muscle fibres had myopathic changes with abnormal central nucleoli and the striated transverse fibres had disappeared in many areas of the sample. Several interstitial foci of muscular necrosis accompanied by phagocytosis and fibrosis were also present.

  16. Experimental carcinogenesis induced by incorporated plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Oghiso, Yoichi [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    The carcinogenic effects of an alpha-emitter, {sup 239}Pu, were investigated by animal experiments as focused on both pulmonary tumors after inhalation exposures to insoluble oxide aerosols and tumor spectra induced by injection of soluble citrate. The life-span study using Wistar strain rats exposed to Pu dioxide aerosols has shown differential dose-related responses of malignancies and histopathological phenotypes of lung tumors, suggesting a threshold dose around 1.0 Gy of the lung dose. As abnormality of tumor-related genes could be supposed for the background of pulmonary carcinogenesis, the mutations of p53 tumor suppressor gene were examined by PCR-SSCP analysis using DNA fragments extracted from lung tumors. While mutations were detected in 23 cases (about 28%) among 82 lung tumors, their relations to either malignancies, histological phenotypes, dose, or oncogenesis are not yet to be elucidated. The life-span study using C3H strain mice injected with Pu citrate has shown contrast dose responses between osteosarcomas and lymphoid tumors around 10 Gy of the skeletal dose, and further indicated specific tumor spectra differed from low LET radiation exposures as shown by much more frequency of B cell type leukemic lymphomas and none of myeloid leukemias. (author)

  17. The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells

    Directory of Open Access Journals (Sweden)

    Seyed Vahid Shetab Boushehri

    2010-10-01

    Full Text Available This is a fullerene-based low toxic nanocationite designed for targeted delivery of the paramagnetic stable isotope of magnesium to the doxorubicin (DXR-induced damaged heart muscle providing a prominent effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 hrs after a single injection (0.03 - 0.1 LD50. Magnesium magnetic isotope effect selectively stimulates the ATP formation in the oxygen-depleted cells due to a creatine kinase (CK and mitochondrial respiratory chain-focusing "attack" of 25Mg2+ released by nanoparticles. These "smart nanoparticles" with membranotropic properties release the overactivating cations only in response to the intracellular acidosis. The resulting positive changes in the energy metabolism of heart cell may help to prevent local myocardial hypoxic (ischemic disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-induced clinical situations including DXR side effects.

  18. Bioeffects of albumin-encapsulated microbubbles and real-time myocardial contrast echocardiography in an experimental canine model

    Directory of Open Access Journals (Sweden)

    P.M.M. Dourado

    2006-06-01

    Full Text Available Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS. In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.

  19. Semen cassiae attenuates myocardial ischemia and reperfusion injury in high-fat diet streptozotocin-induced type 2 diabetic rats.

    Science.gov (United States)

    Fu, Feng; Tian, Fei; Zhou, Heping; Lv, Weifeng; Tie, Ru; Ji, Lele; Li, Rong; Shi, Zhenwei; Yu, Liming; Liang, Xiangyan; Xing, Wenjuan; Xing, Jinliang; Yu, Jun; Sun, Lijun; Zhu, Hailong; Zhang, Haifeng

    2014-01-01

    Obese patients with type 2 diabetes mellitus (T2DM), which is characterized by hyperglycemia, are liable to more severe myocardial infarction. Semen Cassiae is proven to reduce serum lipid levels. This study investigated whether the Semen Cassiae extract (SCE) reduces myocardial ischemia and reperfusion (MI/R) injury with or without diabetes and the underlying mechanisms. The high-fat diet-fed streptozotocin (HFD-STZ) rat model was created as a T2DM model. Normal and DM rats received SCE treatment orally (10 mg/kg/day) for one week. Subsequently these animals were subjected to MI/R. Compared with the normal animals, DM rats showed increased plasma total cholesterol (TC) and triacylglycerol (TG), and more severe MI/R injury and cardiac functional impairment. SCE treatment significantly reduced the plasma TC and TG, improved the instantaneous first derivation of left ventricle pressure and reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase levels, and apoptosis index at the end of reperfusion in diabetic rats. Moreover, SCE treatment increased the antiapoptotic protein Akt and ERK1/2 phosphorylation levels. Pretreatment with a PI3K inhibitor wortmannin or an ERK1/2 inhibitor PD98059 not only blocked Akt and ERK1/2 phosphorylation respectively, but also inhibited the cardioprotective effects of SCE. However, SCE treatment did not show any effects on the MI/R injury in the normal rats. Our data suggest that SCE effectively improves myocardial function and reduces MI/R-induced injury in diabetic but not normal animals, which is possibly attributed to the reduced TC/TG levels and the triggered cell survival signaling Akt and ERK1/2.

  20. 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)

  1. Down-regulation of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor by HEXIM1 attenuates myocardial angiogenesis in hypoxic mice.

    Science.gov (United States)

    Yoshikawa, Noritada; Shimizu, Noriaki; Ojima, Hidenori; Kobayashi, Hiroshi; Hosono, Osamu; Tanaka, Hirotoshi

    2014-10-24

    Pulmonary hypertension (PH) sustains elevation of pulmonary vascular resistance and ultimately leads to right ventricular (RV) hypertrophy and failure and death. Recently, proangiogenic factors hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) have been known to promote left ventricular myocardial angiogenesis and lead to cardiac hypertrophy, and this would be involved in RV hypertrophy of PH patients. Previously, we revealed that overexpression of HEXIM1 prevents endothelin-1-induced cardiomyocyte hypertrophy and hypertrophic genes expression, and that cardiomyocyte-specific HEXIM1 transgenic mice ameliorates RV hypertrophy in hypoxia-induced PH model. Given these results, here we analyzed the effect of HEXIM1 on the expression of HIF-1α and VEGF and on myocardial angiogenesis of RV in PH. We revealed that overexpression of HEXIM1 prevented hypoxia-induced expression of HIF-1α protein and its target genes including VEGF in the cultured cardiac myocytes and fibroblasts, and that cardiomyocyte-specific HEXIM1 transgenic mice repressed RV myocardial angiogenesis in hypoxia-induced PH model. Thus, we conclude that HEXIM1 could prevent RV hypertrophy, at least in part, via suppression of myocardial angiogenesis through down-regulation of HIF-1α and VEGF in the myocardium under hypoxic condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Study of sympathetic nervous function under effort induced ischemia in patients with angina pectoris with I-123 metaiodobenzylguanidine (MIBG) myocardial SPECT images

    International Nuclear Information System (INIS)

    Tanaka, Takeshi; Aizawa, Tadanori; Kato, Kazuzo; Ogasawara, Ken; Sakuma, Toru; Kirigaya, Hajime; Hirosaka, Akira; Igarashi, Masaki

    1990-01-01

    I-123 metaiodobenzylguanidine (MIBG) is a norepinephrine analog, which can be used to study the sympathetic nervous function of the heart. With MIBG myocardial SPECT images sympathetic nervous function under effort induced ischemia were studied in 18 patients with significant coronary artery lesions. In 5 patients with effort induced ischemic region in stress Tl-201 myocardial images rest MIBG images were collected and then exercise stress test was performed. Patients continued exercising for 3 minutes after onset of symptom. Post-stress MIBG images were collected. Definite ischemic region was noted in stress Tl-201 myocardial images, however no differences were noted between rest and post-stress MIBG images. These results suggested that exercise induced ischemia did not enhance release of uptaken MIBG. In 13 patients with significant coronary artery lesions symptom-limited exercise stress test was performed MIBG and Tl-201 were simultaneously injected at onset of symptom and patients continued exercising for an additional one minute. In 6 cases (46%, 6/13) MIBG defects with Tl-201 uptake were noted. These results showed that exercise induced ischemia depressed net MIBG uptake and that sympathetic nervous function (MIBG images) may be more sensitive to ischemic damage than muscle (Tl-201 images). It is suggested that exercise induced ischemia depressed reuptake of norepinephrine at sympathetic nervous endings. MIBG myocardial SPECT images may be useful for evaluating sympathetic nervous function under ischemia. (author)

  3. Insulin Like Growth Factor-1 (IGF-1 Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Nagaraja Haleagrahara

    2011-11-01

    Full Text Available Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1 exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8, in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 µg/kg/day subcutaneously, for 5 and 10 days, isoproterenol (ISO treated (85 mg/kg, subcutaneously for two days and ISO with IGF-1 treated (for 5 and 10 days. Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis.

  4. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  5. Cardioprotective effect of methanolic extract of Marrubium vulgare L. on isoproterenol-induced acute myocardial infarction in rats.

    Science.gov (United States)

    Yousefi, Keyvan; Soraya, Hamid; Fathiazad, Fatemeh; Khorrami, Arash; Hamedeyazdan, Sanaz; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2013-08-01

    Isoproterenol injection (100 mg/kg; sc) produced changes in ECG pattern including ST-segment elevation and suppressed R-amplitude. The methanolic extract of M. vulgare at doses of 10, 20, and 40 mg/kg significantly amended the ECG changes. A severe myocardial necrosis and edematous along with a sharp reduction in the arterial blood pressure, left ventricular contractility (LVdP/dt(max or min)), but a marked increase in the left ventricular end-diastolic pressure (LVEDP) were seen in the isoproterenol group. All parameters were significantly improved by the extract treatment. The extract (10 mg/kg) strongly increased LVdP/dt(max). Similarly, treatment with 40 mg/kg of M. vulgare lowered the elevated LVEDP and the heart to body weight ratio. In addition to in vitro antioxidant activity, the extract suppressed markedly the elevation of malondialdehyde levels both in serum and in myocardium. The results demonstrate that M. vulgare protects myocardium against isoproterenol-induced acute myocardial infarction and suggest that the effects could be related to antioxidant activities.

  6. Coronary vascular age: An alternate means for predicting stress-induced myocardial ischemia in patients with suspected coronary artery disease.

    Science.gov (United States)

    Nappi, Carmela; Gaudieri, Valeria; Acampa, Wanda; Arumugam, Parthiban; Assante, Roberta; Zampella, Emilia; Mannarino, Teresa; Mainolfi, Ciro Gabriele; Imbriaco, Massimo; Petretta, Mario; Cuocolo, Alberto

    2018-01-22

    Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year's scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD). A total of 717 subjects referred to CAC scoring and 82 Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1). Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients. In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

  7. The dimethylhydrazine induced colorectal tumours in rat - experimental colorectal carcinogenesis

    International Nuclear Information System (INIS)

    Perse, M.; Cerar, A.

    2005-01-01

    Animal models of colorectal carcinogenesis represent invaluable research tool for investigating colorectal cancer (CRC). Experimentally induced tumours in laboratory animals provide opportunity for studying certain aspects of tumours that cannot be effectively studied in humans. Significant information on human CRC aetiology or factors influencing it has derived from studies using dimethylhydrazine (DMH) model that is one of the experimental models appreciated for its morphological similarity to human CRC. Today, DMH model represents useful research tool for the studies of colon carcinogens and chemopreventive agents. The review offers insight into morphogenesis and genetic alterations of DMH induced colorectal epithelial tumours in rats. (author)

  8. Rac-Induced Left Ventricular Dilation in Thyroxin-Treated ZmRacD Transgenic Mice: Role of Cardiomyocyte Apoptosis and Myocardial Fibrosis

    Science.gov (United States)

    Elnakish, Mohammad T.; Hassona, Mohamed D. H.; Alhaj, Mazin A.; Moldovan, Leni; Janssen, Paul M. L.; Khan, Mahmood; Hassanain, Hamdy H.

    2012-01-01

    The pathways inducing the critical transition from compensated hypertrophy to cardiac dilation and failure remain poorly understood. The goal of our study is to determine the role of Rac-induced signaling in this transition process. Our previous results showed that Thyroxin (T4) treatment resulted in increased myocardial Rac expression in wild-type mice and a higher level of expression in Zea maize RacD (ZmRacD) transgenic mice. Our current results showed that T4 treatment induced physiologic cardiac hypertrophy in wild-type mice, as demonstrated by echocardiography and histopathology analyses. This was associated with significant increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Conversely, echocardiography and histopathology analyses showed that T4 treatment induced dilated cardiomyopathy along with compensatory cardiac hypertrophy in ZmRacD mice. These were linked with further increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Additionally, there were significant increases in caspase-8 expression and caspase-3 activity. However, there was a significant decrease in p38-MAPK activity. Interestingly, inhibition of myocardial Rac-GTP activity and superoxide generation with pravastatin and carvedilol, respectively, attenuated all functional, structural, and molecular changes associated with the T4-induced cardiomyopathy in ZmRacD mice except the compensatory cardiac hypertrophy. Taken together, T4-induced ZmRacD is a novel mouse model of dilated cardiomyopathy that shares many characteristics with the human disease phenotype. To our knowledge, this is the first study to show graded Rac-mediated O2·− results in cardiac phenotype shift in-vivo. Moreover, Rac-mediated O2·− generation, cardiomyocyte apoptosis, and myocardial fibrosis seem to play a pivotal role in the transition from cardiac hypertrophy to cardiac dilation and failure. Targeting Rac signaling could represent valuable therapeutic strategy not only in saving the

  9. Effect of motion-induced PET-CT misalignment on cardiac function and myocardial blood flow measured using dynamic 15O-water PET

    DEFF Research Database (Denmark)

    Lubberink, Mark; Ebrahimi, M; Harms, Hans

    Aim: Motion-induced PET-CT misalignment artifacts are common in myocardial blood flow (MBF) measurements with 82Rb and 13N-ammonia. For 15O-water, MBF is based on the clearance rate rather than uptake of the tracer. The clearance rate is determined by the shape of the time-activity curve, not its...

  10. Experimental synchronization of circuit oscillations induced by common telegraph noise.

    Science.gov (United States)

    Nagai, Ken; Nakao, Hiroya

    2009-03-01

    Experimental realization and quantitative investigation of common-noise-induced synchronization of limit-cycle oscillations subject to random telegraph signals are performed using an electronic oscillator circuit. Based on our previous formulation [K. Nagai, Phys. Rev. E 71, 036217 (2005)], dynamics of the circuit is described as random-phase mappings between two limit cycles. Lyapunov exponents characterizing the degree of synchronization are estimated from experimentally determined phase maps and compared with linear damping rates of phase differences measured directly. Noisy on-off intermittency of the phase difference as predicted by the theory is also confirmed experimentally.

  11. Premature Ventricular Contractions (PVCs Induced by Administration of Cilostazol after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Lihua Zhong

    2013-02-01

    Full Text Available Cilostazol is a phosphodiesterase III inhibitor, which was approved by FDA (food and drug administration for intermittent claudication in 1999. What made it known to cardiologists is the Cilostazol for Restenosis Trial (CREST, in which cilostazol was shown to significantly lower binary restenosis rate. Here we reported one case of acquired premature ventricular contractions (PVCs during taking cilostazol. A 68-year-old male patient was diagnosed acute myocardial infarction and given percutaneous coronary intervention (PCI. It turned out there was thrombi in the distal right coronary artery. The patient was discharged taking cilostazol (100mg Bid together with aspirin and clopidogrel. On follow-up, there were PVCs coming up (more than 27000 beats in 24-hour electrocardiography and cilostazol was discontinued afterwards. After taking metoprolol (25 mg, Tid for one week, the PVCs were decreased significantly, 600 beats/24 hours. In our case, the PVCs are obviously related to cilostazol and probably the safety of cilostazol in patients having a history of myocardial infarction or malignant arrhythmias should be reevaluated.

  12. Thallium-201 myocardial imaging during coronary vasodilation induced by oral dipyridamole

    International Nuclear Information System (INIS)

    Gould, K.L.; Sorenson, S.G.; Albro, P.; Caldwell, J.H.; Chaudhuri, T.; Hamilton, G.W.

    1986-01-01

    Myocardial perfusion imaging of 201 TI injected during maximum exercise has been an important diagnostic tool for coronary artery disease. Pharmacologic coronary vasodilation by i.v. infusion of dipyridamole may be used in lieu of exercise stress for purposes of diagnostic perfusion imaging. However, i.v. dipyridamole is not currently available from commercial sources for widespread routine use. Accordingly, this study was carried out in order to determine whether high dose, oral dipyridamole would be useful as a coronary vasodilator for purposes of diagnostic perfusion imaging. Fifty-eight patients undergoing diagnostic coronary arteriography also had myocardial perfusion imaging with 201TI under conditions of rest, maximum exercise stress, and high dose oral dipyridamole. Of those patients who had a defect on exercise thallium images, 75% also had a perfusion defect on thallium images after high dose oral dipyridamole. These results indicate that oral dipyridamole causes sufficient coronary arteriolar vasodilation and increase of coronary flow in nonstenotic arteries to identify perfusion defects comparable to those seen on maximum exercise stress in at least 75% of cases. In 25% of patients with exercise defects, no perfusion defect was seen after oral dipyridamole. Thus, oral dipyridamole is a potent coronary vasodilator, comparable to exercise stress in most cases, but in a minority of patients may not be comparable to exercise stress

  13. Ultrasound v. sham ultrasound for experimentally induced delayed ...

    African Journals Online (AJOL)

    In a double-blind controlled trial, delayed-onset muscle soreness (DOMS) was experimentally induced in both bicep muscles of 15 females. Sham US was applied to one bicep (n=15 biceps) and pulsed active US to the other bicep (n=15 biceps) of each participant, 48 and 72 h after induction of DOMS. Primary and ...

  14. Experimental and analytical studies on pedestrian induced footbridge vibrations

    DEFF Research Database (Denmark)

    Gudmundsson, Gudmundur Valur; Ingólfsson, Einar Thór; Einarsson, Baldvin

    2007-01-01

    This paper presents results from experimental study on human-induced vibrations of three lively footbridges in Reykjavik. The project was funded by the Icelandic Public Roads Administration with two main focus areas; validating the FE-models used at the design stage in terms of dynamic...

  15. Cholescintigraphy in experimentally induced obstructive and parenchymatous jaundice

    International Nuclear Information System (INIS)

    Baehre, M.; Biersack, H.J.; Hofmann, S.; Winkler, C.

    1979-01-01

    Animal studies have been performed in 30 dogs in order to obtain information concerning typical patterns of cholescintigraphy in acute obstructive jaundice. In 14 the choledochus was ligated and in 16 galactosamine-hepatitis was induced as an experimental model for parenchymatous jaundice. The results suggest a number of diagnostic criteria in obstructive disease. (Auth.)

  16. Prolonged drug-induced hypothermia in experimental stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Jørgensen, Henrik Stig; Reith, Jakob

    2007-01-01

    In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia...

  17. Experimental observation of direct current voltage-induced phase ...

    Indian Academy of Sciences (India)

    Experimental observation of direct current voltage-induced phase synchronization. HAIHONG LI1, WEIQING LIU1,2, QIONGLING DAI1 and JINGHUA XIAO1. 1School of Science, Beijing University of Posts and Telecommunications, Beijing 100876,. China. 2School of Science, Jiangxi University of Science and Technology, ...

  18. Relationship between regional myocardial blood flow and thallium-201 distribution in the presence of coronary artery stenosis and dipyridamole-induced vasodilation.

    Science.gov (United States)

    Mays, A E; Cobb, F R

    1984-01-01

    This study assesses the relationship between the distribution of thallium-201 and myocardial blood flow during coronary vasodilation induced by intravenous dipyridamole in canine models of partial and complete coronary artery stenosis. 10 dogs were chronically instrumented with catheters in the left atrium and aorta and with a balloon occluder and electromagnetic flow probe on the proximal left circumflex coronary artery. Regional myocardial blood flow was measured during control conditions with radioisotope-labeled microspheres, and the phasic reactive hyperemic response to a 20-s transient occlusion was then recorded. Dipyridamole was then infused intravenously until phasic coronary blood flow increased to match peak hyperemic values. The left circumflex coronary artery was either partially occluded to reduce phasic blood flow to control values (group 1) or it was completely occluded (group 2), and thallium-201 and a second microsphere label were injected. 5 min later, the animals were sacrificed, the left ventricle was sectioned into 1-2-g samples, and thallium-201 activity and regional myocardial blood flow were measured. Curvilinear regression analyses between thallium-201 localization and myocardial blood flow during dipyridamole infusion demonstrated a slightly better fit to a second- as compared with a first-order model, indicating a slight roll-off of thallium activity as myocardial blood flow increases. During the dipyridamole infusion, the increases in phasic blood flow, the distributions of regional myocardial blood flow, and the relationships between thallium-201 localization and regional blood flow were comparable to values previously observed in exercising dogs with similar occlusions. These data provide basic validation that supports the use of intravenous dipyridamole and thallium-201 as an alternative to exercise stress and thallium-201 for evaluating the effects of coronary occlusive lesions on the distribution of regional myocardial blood flow

  19. Downregulation of adiponectin induced by tumor necrosis factor α is involved in the aggravation of posttraumatic myocardial ischemia/reperfusion injury.

    Science.gov (United States)

    Liu, Shaowei; Yin, Tao; Wei, Xufeng; Yi, Wei; Qu, Yan; Liu, Yi; Wang, Rutao; Lian, Kun; Xia, Chenhai; Pei, Haifeng; Sun, Lu; Ma, Yanzhuo; Lau, Wayne Bond; Gao, Erhe; Koch, Walter J; Wang, Haichang; Tao, Ling

    2011-08-01

    Recent clinical observations have indicated that nonlethal mechanical trauma significantly increases myocardial infarction risk even in the presence of completely normal coronary arteries. We investigated the molecular mechanisms responsible for exacerbation of ischemic myocardial injury after nonlethal mechanical trauma with a special focus on the role of tumor necrosis factor α and its potential downstream effector adiponectin, a novel adipokine with anti-inflammatory and cardioprotective properties. Laboratory study. University research unit. Male adult adiponectin knockout mice and wild-type mice. The animals were subjected to nonlethal mechanical trauma using the Noble-Collip drum (40 rpm ± 5 mins) followed by myocardial ischemia/reperfusion injury 7 days posttrauma. We also investigated the effects of neutralizing tumor necrosis factor α with etanercept and exogenous adiponectin supplementation on ischemic myocardial injury after trauma. Trauma significantly sensitized myocardium to ischemia/reperfusion injury as evidenced by increased apoptosis, enlarged infarct size, and decreased cardiac function. Plasma adiponectin concentrations were reduced after traumatic injury (the nadir occurring 3 days posttrauma), an effect abrogated by etanercept-mediated tumor necrosis factor α blockade. The downregulation of adiponectin was accompanied by increased myocardial superoxide and nitric oxide generation and peroxynitrite formation. Both etanercept and exogenous adiponectin supplementation (on day 3 posttrauma or 10 mins before reperfusion on day 7 posttrauma) markedly inhibited oxidative/nitrative stress and ischemia/reperfusion injury in posttraumatic ischemic/reperfused hearts of wild-type mice, whereas only adiponectin supplementation (but not tumor necrosis factor α inhibition) substantially attenuated posttraumatic ischemia/reperfusion injury in adiponectin knockout mice. Tumor necrosis factor α-induced downregulation of adiponectin and the resultant

  20. [Effect of enalapril maleate and lozartan on the size of experimental myocardial infarction, hemoglobin affinity to oxygen and various parameters of lipid peroxidation].

    Science.gov (United States)

    Gatsura, S V; Zinchuk, V V

    2004-01-01

    The intravenous injections of enalapril maleate (0.1 and 0.5 mg/kg) and losartan (0.5 and 2.5 mg/kg) produced a 22-32% decrease in the size of myocardial infarction in rats with coronary ligation. This was accompanied by inhibition of the lipid peroxidation as revealed by the MDA test and Fe2+ induced chemiluminescence. Both drugs also increased the oxygen affinity of hemoglobin in the P50 test in vitro. Enalapril did not significantly alter the MDA level and superoxide dismutase (SOD) activity in the whole human blood. In contrast, losartan reliably inhibited SOD activity.

  1. Endothelin receptor mediated Ca(2+) signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat

    DEFF Research Database (Denmark)

    Kristiansen, Sarah Brøgger; Haanes, Kristian A.; Sheykhzade, Majid

    2017-01-01

    BACKGROUND: Acute myocardial infarction is one of the leading causes of death. It is caused by a blockage of a coronary artery leading to reduced blood flow to the myocardium and hence ischemic damage. In addition, a second wave of damage after the flow has been restored, named reperfusion injury...... greatly exacerbate the damage. For the latter, no medical treatment exist. In this study the aim was to characterize Ca(2+) sensitivity in coronary arteries following experimental ischemia/reperfusion injury. METHODS: Arteries were isolated from hearts exposed to a well-established rat ischemia/reperfusion...... presumably through voltage-gated Ca(2+) channels (VGCC). In addition, we show that there is an increase in the stretch-induced tone after ischemia/reperfusion, and that this increase in tone is independent of the ETB-R upregulation. CONCLUSION: Our data support the theory that ischemia/reperfusion may induce...

  2. Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice

    Directory of Open Access Journals (Sweden)

    Fang Li

    2016-01-01

    Full Text Available Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin-light chains 1, cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF, cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB to nucleus and formation of LC3-II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP-1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy-oxidative stress-inflammation-cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly.

  3. Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Inubushi, Masayuki; Dahlbom, Magnus; Schelbert, Heinrich R. [Department of Molecular and Medical Pharmacology, University of California Los Angeles David Geffen School of Medicine, B2-086 J CHS, Box 951735, CA 90095-1735, Los Angeles (United States); Jordan, Maria C.; Roos, Kenneth P.; Ross, Robert S. [Department of Physiology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA (United States); Chatziioannou, Arion F.; Stout, David B. [The Crump Institute for Molecular Imaging, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA (United States)

    2004-01-01

    We explored the feasibility of imaging myocardial perfusion and of demonstrating the flow changes in response to reduction of cardiac work non-invasively in anesthetized mice using high spatial resolution, dedicated small-animal positron emission tomography (microPET). In 31 C57BL/6 mice anesthetized with pentobarbital or isoflurane, {sup 13}N-ammonia was injected intravenously and images were recorded with microPET from 4 to 20 min. Fifteen mice (group 1) were studied consecutively at baseline (BL) and after reduction of heart rate (HR) with intraperitoneal injection of clonidine (CLN) to investigate effects of CLN-induced reduction of cardiac work on myocardial {sup 13}N-ammonia uptake. Eight mice (group 2) were imaged repeatedly at BL and eight mice (group 3) twice after CLN to examine reproducibility. Total myocardial {sup 13}N-ammonia accumulation was determined from the transaxial images and normalized for injected dose (%ID). HR was 412{+-}97 beats/min at BL and 212{+-}44 beats/min after CLN (P<0.0001). In group 1, the %ID significantly decreased from 1.50%{+-}0.27% at BL to 1.29%{+-}0.28% after CLN (P<0.0001). In groups 2 and 3, reproducibility of %ID was good (y=0.96x+0.105, SEE=0.212%, r{sup 2}=0.749, P<0.0001). In conclusion, {sup 13}N-ammonia microPET imaging demonstrated non-invasively a reduction of myocardial perfusion induced by clonidine in mice. We believe this study is of importance as the first report on myocardial perfusion imaging and flow validation in in vivo mouse hearts with a left ventricular size of only 5 mm using {sup 13}N-ammonia and PET. MicroPET will aid in elucidating cardiac pathophysiology in transgenic mice and monitoring effects of gene therapies on myocardial perfusion. (orig.)

  4. Myocardial contusion

    Science.gov (United States)

    ... 000202.htm Myocardial contusion To use the sharing features on this page, please enable JavaScript. Myocardial contusion ... Wear a seat belt when driving. Choose a car with air bags. Take steps to ensure safety when working at heights. Alternative Names Blunt myocardial ...

  5. Adverse postresuscitation myocardial effects elicited by buffer-induced alkalemia ameliorated by NHE-1 inhibition in a rat model of ventricular fibrillation.

    Science.gov (United States)

    Lamoureux, Lorissa; Radhakrishnan, Jeejabai; Mason, Thomas G; Kraut, Jeffrey A; Gazmuri, Raúl J

    2016-11-01

    Major myocardial abnormalities occur during cardiac arrest and resuscitation including intracellular acidosis-partly caused by CO 2 accumulation-and activation of the Na + -H + exchanger isoform-1 (NHE-1). We hypothesized that a favorable interaction may result from NHE-1 inhibition during cardiac resuscitation followed by administration of a CO 2 -consuming buffer upon return of spontaneous circulation (ROSC). Ventricular fibrillation was electrically induced in 24 male rats and left untreated for 8 min followed by defibrillation after 8 min of cardiopulmonary resuscitation (CPR). Rats were randomized 1:1:1 to the NHE-1 inhibitor zoniporide or vehicle during CPR and disodium carbonate/sodium bicarbonate buffer or normal saline (30 ml/kg) after ROSC. Survival at 240 min declined from 100% with Zoniporide/Saline to 50% with Zoniporide/Buffer and 25% with Vehicle/Buffer (P = 0.004), explained by worsening postresuscitation myocardial dysfunction. Marked alkalemia occurred after buffer administration along with lactatemia that was maximal after Vehicle/Buffer, attenuated by Zoniporide/Buffer, and minimal with Zoniporide/Saline [13.3 ± 4.8 (SD), 9.2 ± 4.6, and 2.7 ± 1.0 mmol/l; P ≤ 0.001]. We attributed the intense postresuscitation lactatemia to enhanced glycolysis consequent to severe buffer-induced alkalemia transmitted intracellularly by an active NHE-1. We attributed the worsened postresuscitation myocardial dysfunction also to severe alkalemia intensifying Na + entry via NHE-1 with consequent Ca 2+ overload injuring mitochondria, evidenced by increased plasma cytochrome c Both buffer-induced effects were ameliorated by zoniporide. Accordingly, buffer-induced alkalemia after ROSC worsened myocardial function and survival, likely through enhancing NHE-1 activity. Zoniporide attenuated these effects and uncovered a complex postresuscitation acid-base physiology whereby blood pH drives NHE-1 activity and compromises mitochondrial function and integrity along

  6. NADPH Oxidase-4 Driven Cardiac Macrophage Polarization Protects Against Myocardial Infarction–Induced Remodeling

    Directory of Open Access Journals (Sweden)

    Heloise Mongue-Din, PharmD, PhD

    2017-12-01

    Full Text Available The reactive oxygen species–generating enzyme NADPH oxidase 4 (Nox4 is up-regulated in the heart after myocardial infarction (MI. Mice with cardiomyocyte-targeted Nox4 overexpression (TG displayed increased macrophages in the heart at baseline, with skewing toward an M2 phenotype compared with wild-type controls (WT. After MI, TG mice had a higher proportion of M2 macrophages along with higher survival, decreased cardiac remodeling, and better contractile function than wild-type mice. The post-MI increase in cardiac matrix metalloproteinase–2 activity was substantially blunted in TG mice. These results indicate that cardiomyocyte Nox4 modulates macrophage polarization toward an M2 phenotype, resulting in improved post-MI survival and remodeling, likely through the attenuation of cardiac matrix metalloproteinase–2 activity.

  7. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction

    International Nuclear Information System (INIS)

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schark, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-01-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occulsion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p=0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes acumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

  8. The effect of ibuprofen on accumulation of 111In-labeled platelets and leukocytes in experimental myocardial infarction

    International Nuclear Information System (INIS)

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schork, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-01-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p . 0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

  9. Protective Role of N-Acetylcysteine on Isoprenaline-Induced Myocardial Injury: Histological, Immunohistochemical and Morphometric Study.

    Science.gov (United States)

    Zaki, Sherif Mohamed; Abdalla, Ibrahim Labib; Sadik, Abir Oueida El; Mohamed, Enas Ahmad; Kaooh, Sarah

    2018-02-01

    Several researchers studied the protective effect of the N-acetylcysteine (NAC) when it was given before the induction of myocardial infarction (MI). Other researchers studied such protective effect when it was before done and after done of the MI. The missing data are the comparison between the protective effect of NAC before myocardial injury with its protective effect both before and after myocardial injury. The aim of the study was to compare the cardioprotective effect of NAC on the isoprenaline-induced myocardial injury before the isoprenaline (ISP) injection with its protective effect both before and after the ISP injection. This study was applied over both short and long time periods. A total of 90 male adult Wistar albino rats were used in the study. The rats were divided into four groups: control group, ISP-treated group, NAC-pretreated group and NAC-pre-& posttreated group. Based on the duration of the experiment, the second and third groups were further subdivided into a and b groups. Histological, immunohistochemical and histomorphometric analysis were used. The myocytes in the ISP-treated groups were fragmented, disrupted with karyolysis. The blood vessels were dilated, congested and associated with blood extravasation, interstitial edema and cellular inflammatory infiltration. Much improvement was observed in the NAC-pretreated group. Focal degeneration was detected in the muscle fibers. The capillaries were normal. Minimal blood extravasation and cellular infiltration were seen. The cardiac muscle fibers in the NAC-pre-& posttreated group were regularly arranged. The mean collagen fiber area percent of the ISP-treated groups was significantly higher by 8.3-folds and 10.1-folds as compared with that of the control group and was also higher by 5.5-folds and 6.8-folds as compared with that of the NAC-pre-&posttreated groups. The α-SMA area percent in the ISP-treated groups was significantly higher by 12.2-folds and 23.9-folds as compared with that of

  10. Associations between positive emotional well-being and stress-induced myocardial ischemia: Well-being scores predict exercise-induced ischemia.

    Science.gov (United States)

    Feigal, Jacob P; Boyle, Stephen H; Samad, Zainab; Velazquez, Eric J; Wilson, Jennifer L; Becker, Richard C; Williams, Redford B; Kuhn, Cynthia M; Ortel, Thomas L; Rogers, Joseph G; O'Connor, Christopher M; Jiang, Wei

    2017-02-01

    Depressive symptoms have been associated with myocardial ischemia induced by mental (MSIMI) and exercise (ESIMI) stress in clinically stable ischemic heart disease (IHD) patients, but the association between positive emotions and inducible ischemia is less well characterized. The objective of this study was to examine the associations between ratings of well-being and stress-induced ischemia. Subjects were adult patients with documented IHD underwent mental and exercise stress testing for the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) trial. The General Well-Being Schedule (GWBS), with higher scores reflecting greater subjective well-being, and the Center for Epidemiologic Studies Depression Scale (CES-D) were obtained from the REMIT participants. Echocardiography was used to measure ischemic responses to mental stress and Bruce protocol treadmill exercise testing. Data were analyzed using logistic regression adjusting for age, sex, resting left-ventricular ejection fraction (LVEF), and resting wall motion score index, as well as health-related behaviors. GWBS scores were obtained for 210 individuals, with MSIMI present in 92 (43.8%) and ESIMI present in 64 (30.5%). There was a significant inverse correlation between GWBS-PE (Positive Emotion subscale) scores and probability of ESIMI (OR=0.55 (95%CI 0.36-0.83), p=0.005). This association persisted after additional control for CESD subscales measuring negative and positive emotions and for variables reflecting health-related behaviors. A similar inverse correlation between GWBS-PE and MSIMI was observed, but did not reach statistical significance (OR=0.81 (95%CI 0.54-1.20), p=0.28). This is, to our knowledge, the first study demonstrating that greater levels of self-reported positive emotions are associated with a lower likelihood of ESIMI among patients with known IHD. Our results highlight the important interface functions of the central nervous and cardiovascular systems and underscore

  11. Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI

    Directory of Open Access Journals (Sweden)

    Chandrasekaran Suresh

    2007-02-01

    Full Text Available Abstract Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy.

  12. Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy.

    Science.gov (United States)

    Ge, Lan; Zhou, Xin; Ji, Wen-Jie; Lu, Rui-Yi; Zhang, Yan; Zhang, Yi-Dan; Ma, Yong-Qiang; Zhao, Ji-Hong; Li, Yu-Ming

    2015-03-01

    Emerging evidence suggests a potential role of neutrophil extracellular traps (NETs) in linking sterile inflammation and thrombosis. We hypothesized that NETs would be induced during myocardial ischemia-reperfusion (I/R), and NET-mediated microthrombosis may contribute to myocardial "no-reflow". Male Wistar rats were randomly divided into I/R control, DNase (DNase I, 20 μg/rat), recombinant tissue-type plasminogen activator (rt-PA, 420 μg/rat), DNase + rt-PA, and sham control groups after 45-min myocardial ischemia. In situ NET formation, the anatomic "no re-flow" area, and infarct size were evaluated immediately after 3 h of reperfusion. Long-term left ventricular (LV) functional and histological analyses were performed 45 days after operation. Compared with the I/R controls, the DNase + rt-PA group exhibited reduced NET density [8.38 ± 1.98 vs. 26.86 ± 3.07 (per 200 × field), P injury-induced LV remodeling (LV ejection fraction: 64.22 ± 3.37 vs. 33.81 ± 2.98%, P reperfusion strategy (DNase I + rt-PA), which might be a promising option for the treatment of myocardial I/R injury and coronary no-reflow. Copyright © 2015 the American Physiological Society.

  13. Extracellular talaporfin sodium-induced photosensitization reaction with various albumin animal species on myocardial cells in vitro

    Science.gov (United States)

    Ogawa, Emiyu; Arai, Tsunenori

    2017-02-01

    It is reported that the albumin has different structure among animal species. We have proposed a new methodology of cardiac ablation using talaporfin sodium-induced photosensitization reaction with short drug-light interval to realize immediate and permanent therapeutic effect by singlet oxygen production mainly in the interstitial space. The photosensitization reaction efficacy with different animal species should be investing to consider the optimal animal therapeutic model to evaluate the therapeutic effect of new cardiac ablation methodology. We studied the cell-killing efficacy of extracellular talaporfin sodium-induced photosensitization reaction using talaporfin sodium on myocardial cells in vitro with different albumin animal species: human, canine, bovine, and porcine serum albumin. We obtained that the albumin concentration tendency on the binding ratio and cell lethality was different among the animal species but there was no correlation between binding ratio and cell lethality. We found that the cell lethality dependence on albumin concentration showed 2 different groups, human-canine and bovine-porcine. We think that the canine might be useful as a therapeutic animal model since the cytotoxicity tendency on albumin concentration was similar with that of human albumin. These cell lethality tendency difference would be suggested to explain by the existence of the diazepam site that talaporfin sodium binds mainly.

  14. {sup 99m}Tc-annexin V and {sup 111}In-antimyosin antibody uptake in experimental myocardial infarction in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarda-Mantel, Laure; Rouzet, Francois; Martet, Genevieve; Raguin, Olivier; Vrigneaud, Jean-Marc; Guludec, Dominique Le [Bichat Hospital AP-HP, EA 3512, Nuclear Medicine Department, Paris (France); Michel, Jean-Baptiste; Louedec, Liliane [INSERM U460, UFR Bichat, Paris (France); Vanderheyden, Jean-Luc [Theseus Imaging Corporation, Boston, MA (United States); Hervatin, Florence [Bichat Hospital AP-HP, EA 3512, Nuclear Medicine Department, Paris (France); CGA/SHFS, Orsay (France); Khaw, Ban An [Bouve College of Pharmacy and Health Sciences, Center for Drug Targeting and Analysis, Boston, MA (United States)

    2006-03-15

    {sup 99m}Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ({sup 111}In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain). The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats. All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1{+-}0.6 versus 1.5{+-}0.3 (p=0.001) for ANX and 1.99{+-}0.44 versus 1.01{+-}0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6{+-}0.9 versus 5.0{+-}1.8 at 24 h), while Apostain staining was very low (0.06{+-}0.06% of cells). In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas. (orig.)

  15. Regulation of Na+-K+-ATPase effected high glucose-induced myocardial cell injury through c-Src dependent NADPH oxidase/ROS pathway.

    Science.gov (United States)

    Yan, Xiaofei; Xun, Meng; Dou, Xiaojuan; Wu, Litao; Han, Yan; Zheng, Jin

    2017-08-15

    Depressed Na + /K + -ATPase activity has long been reported to be involved in diabetic-related cardiomyocyte death and cardiac dysfunction. However, the nature of directly regulating Na + -K + -ATPase in diabetic-related myocardial diseases remains unknown. Hyperglycemia is believed as one of major factors responsible for diabetic-related myocardial apoptosis and dysfunction. In this study, whether inhibiting Na + -K + -ATPase by ouabain or activating Na + -K + -ATPase by DRm217 has functions on high glucose (HG) -induced myocardial injury was investigated. Here we found that addition of DRm217 or ouabain to HG-treated cells had opposite effects. DRm217 decreased but ouabain increased HG-induced cell injury and apoptosis. This was mediated by changing Na + -K + -ATPase activity and Na + -K + -ATPase cell surface expression. The inhibition of Na + -K + -ATPase endocytosis alleviated HG-induced ROS accumulation. Na + -K + -ATPase·c-Src dependent NADPH oxidase/ROS pathway was also involved in the effects of ouabain and DRm217 on HG-induced cell injury. These novel results may help us to understand the important role of the Na + -K + -ATPase in diabetic cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction.

    Science.gov (United States)

    Flores, Lucinar J; Figueroa, Diego; Sanches, Iris C; Jorge, Luciana; Irigoyen, Maria-Cláudia; Rodrigues, Bruno; De Angelis, Kátia

    2010-07-01

    The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 microg/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.

  17. Cardiac function improved by sarcoplasmic reticulum Ca2+-ATPase overexpression in a heart failure model induced by chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Wei XIN

    2011-04-01

    Full Text Available Objective Chronic myocardial ischemia(CMI has become an important cause of heart failure(HF.The aim of present study was to examine the effects of Sarco-endoplasmic reticulum calcium ATPase(SERCA2a gene transfer in HF model in large animal induced by CMI.Methods HF was reproduced in minipigs by ligating the initial segment of proximal left anterior descending(LAD coronary artery with an ameroid constrictor to produce progressive vessel occlusion and ischemia.After confirmation of myocardial perfusion defect and cardiac function impairment by SPECT and echocardiography in the model,animals were divided into 4 groups: HF group;HF+enhanced green fluorescent protein(EGFP group;HF+SERCA2a group;and sham operation group as control.rAAV1-EGFP and rAAV1-SERCA2a(1×1012 vg for each animal were directly and intramyocardially injected to the animals of HF+EGFP and HF+SERCA2a groups.Sixty days after the gene transfer,the expression of SERCA2a at the protein level was examined by Western blotting and immunohistochemistry,the changes in cardiac function were determined by echocardiographic and hemodynamic analysis,and the changes in serum inflammatory and neuro-hormonal factors(including BNP,TNF-a,IL-6,ET-1 and Ang II were determined by radioimmunoassay.Results Sixty days after gene transfer,LVEF,Ev/Av and ±dp/dtmax increased significantly(P < 0.05,along with an increase of SERCA2a protein expression in the ischemic myocardium(PP < 0.05,accompanied by a significant decrease of inflammatory and neural-hormonal factors(PP < 0.05 in HF+SERCA2a group as compared with HF/HF+EGFP group.Conclusions Overexpression of SERCA2a may significantly improve the cardiac function of the ischemic myocardium of HF model induced by CMI and reverse the activation of neural-hormonal factors,implying that it has a potential therapeutic significance in CMI related heart failure.

  18. Microcirculation alterations in experimentally induced gingivitis in dogs.

    Science.gov (United States)

    Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

    2017-01-01

    The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

  19. Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin.

    Science.gov (United States)

    Kozàkovà, Michaela; Buralli, Simona; Palombo, Carlo; Bernini, Giampaolo; Moretti, Angelica; Favilla, Stefania; Taddei, Stefano; Salvetti, Antonio

    2003-02-01

    A disproportionate accumulation of fibrillar collagen is a characteristic feature of hypertensive heart disease, but the extent of myocardial fibrosis may differ in different models of hypertension. In experimental studies, aldosterone and endothelins emerge as important determinants of myocardial fibrosis. Changes in myocardial extracellular matrix and collagen deposition can be estimated noninvasively by analysis of the ultrasonic backscatter signal, which arises from tissue heterogeneity within the myocardium and describes myocardial texture. This study was designed to investigate the relations between myocardial integrated backscatter and circulating aldosterone and immunoreactive endothelin in human hypertension. The study population consisted of 56 subjects: 14 healthy normotensive volunteers and 42 hypertensive patients (14 with primary aldosteronism, 7 with renovascular hypertension, and 21 with essential hypertension). The patients with essential and secondary hypertension were matched for age, gender, body mass index, and blood pressure. Myocardial integrated backscatter at diastole was 19.8+/-2.0 and 20.8+/-2.9 decibels in normotensive control subjects and patients with essential hypertension and significantly higher in patients with primary aldosteronism (27.4+/-3.8 decibels, P<0.01) and renovascular hypertension (26.8+/-4.8 decibels, P<0.01). In the population as a whole, as well as in the hypertensive subpopulation, myocardial integrated backscatter was directly related to plasma aldosterone (r=0.73 and 0.71, P<0.01 for both) and immunoreactive endothelin (r=0.60 and 0.56, P<0.01 for both). The data of this study suggest that in human hypertension, circulating aldosterone and immunoreactive endothelin may induce alterations in left ventricular myocardial texture, possibly related to increased myocardial collagen content.

  20. Fentanyl Ameliorates Severe Acute Pancreatitis-Induced Myocardial Injury in Rats by Regulating NF-κB Signaling Pathway.

    Science.gov (United States)

    Wang, Yayun; Chen, Manhua

    2017-07-06

    BACKGROUND Acute pancreatitis (AP) is a sudden inflammation of the pancreas. It results in multiple, severe complications, and 15-20% of patients develop severe acute pancreatitis (SAP) with mortality as high as 30%. Consequently, it is imperative to develop an effective therapy for SAP. MATERIAL AND METHODS We used 30 adult male Sprague Dawley (SD) rats. Rats were randomly divided into 3 groups - sham, SAP, and fentanyl+SAP - with 10 rats in each group. An automatic biochemical analyzer was used to analyze the concentration of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay was applied to assess the cell apoptosis rate. Pathological changes in pancreas/heart were detected with hematoxylin and eosin (HE) staining. Western immunoblot assay was used to analyze protein levels of interleukin (IL)-1β, IL-6, and IκB. RESULTS Fentanyl pre-treatment inhibits SAP-induced elevation of CK-MB/LDH concentrations in serum. Compared with the sham group, SAP generates a higher brown/yellow staining rate, which is abated by fentanyl. In the pancreas, SAP generated more serious interstitial edema/hemorrhage and fat necrosis than in the sham group, which are attenuated by fentanyl. Likewise, compared to the sham group, SAP generates swelled/disordered myocardial fibers and congested blood vessels in myocardium, which are ameliorated by fentanyl. In the sham group, there was little IL-1β/IL-6, and fentanyl significantly inhibited SAP-induced up-regulation of IL-1β/IL-6 levels. Compared with the sham group, SAP significantly reduced IκB level, which was rescued by fentanyl. CONCLUSIONS Fentanyl effectively alleviates SAP-induced pancreas and heart injuries through regulating the nuclear factor-κB (NF-κB) signaling pathway.

  1. Effects of taurine on myocardial cGMP/cAMP ratio, antioxidant ability, and ultrastructure in cardiac hypertrophy rats induced by isoproterenol.

    Science.gov (United States)

    Yang, Qunhui; Yang, Jiancheng; Wu, Gaofeng; Feng, Ying; Lv, Qiufeng; Lin, Shumei; Hu, Jianmin

    2013-01-01

    Taurine is the most abundant free amino acid in the human body and accounts for more than 50% of the total amino acid pool in the mammalian heart. To investigate the preventive effects of taurine on cardiac hypertrophy in rats, myocardial injury was established by hypodermic injection of isoprenaline (ISO) (10 mg/kg d) for 7 days. The preventive effects of taurine (100 mg/kg d, 200 mg/kg d, and 300 mg/kg d, i.p) on heart coefficient; ultrastructure of cardiac muscle; the levels of creatine kinase heart isoenzyme (CK-MB), cAMP, and cGMP; and antioxidant ability were investigated. The results showed that taurine could significantly prevent the increase of heart coefficient induced by ISO. Compared with the model group, 100 mg/kg and 200 mg/kg taurine significantly decrease the levels of cAMP and cGMP, while 300 mg/kg taurine could significantly decrease the levels of cAMP in myocardium, and all the three concentrations of taurine could significantly increase the ratio of cGMP/cAMP. The level of serum CK-MB was significantly increased by ISO; 200 mg/kg taurine could significantly decrease it, but 100 mg/kg and 300 mg/kg taurine had no significant effect. As for the antioxidant ability, ISO administration could significantly increase the myocardial level of MDA but had no significant effects on the myocardial levels of SOD, GSH, GSH-Px, and T-AOC. However, taurine administration could significantly decrease the myocardial level of MDA and increase the levels of GSH and T-AOC compared with the model group. The serum levels of SOD, GSH-Px, GSH, and T-AOC were significantly reduced by ISO administration, but the level of MDA showed no significant changes compared with the control group. Taurine administration could significantly increase the serum levels of SOD, GSH-Px, GSH, and T-AOC and decrease the level of MDA compared with the model group. All the results indicated that 200 mg/kg taurine had better effects. The ultrastructure of cardiomyocytes showed that taurine

  2. Stress-induced myocardial ischemia is associated with early post-stress left ventricular mechanical dyssynchrony as assessed by phase analysis of {sup 201}Tl gated SPECT myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chien-Cheng; Shen, Thau-Yun [Show Chwan Memorial Hospital, Department of Cardiology, Changhua (China); Chang, Ming-Che [Changhua Christian Hospital, Department of Nuclear Medicine, Changhua (China); Hung, Guang-Uei [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Changhua (China); China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China); Chen, Wan-Chen [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Changhua (China); Kao, Chia-Hung [China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China); Chen, Ji [Emory University School of Medicine, Department of Radiology and Imaging Sciences, Atlanta, GA (United States)

    2012-12-15

    In {sup 201}Tl SPECT myocardial perfusion imaging (MPI) data are acquired shortly after the stress injection to assess early post-stress left ventricle (LV) function. The purpose of this study was to use {sup 201}Tl SPECT MPI to investigate whether stress-induced myocardial ischemia is associated with LV mechanical dyssynchrony. Enrolled in the study were 75 patients who were referred for dipyridamole stress and rest {sup 201}Tl gated SPECT MPI. The early post-stress scan was started 5 min after injection, and followed by the rest scan 4 h later. The patients were divided into three groups: ischemia group (N = 25, summed stress score, SSS, {>=}5, summed rest score, SRS, <5), infarct group (N = 16, SSS {>=}5, SRS {>=}5) and normal group (N = 34, SSS <5, SRS <5). LV dyssynchrony parameters were calculated by phase analysis, and compared between the stress and rest images. In the ischemia group, LV dyssynchrony was significantly larger during stress than during rest. On the contrary, LV dyssynchrony during stress was significantly smaller than during rest in the normal and infarct groups. LV dyssynchrony during rest was significantly larger in the infarct group than in the normal and ischemia groups. There were no significant differences in LV dyssynchrony during rest between the normal and ischemia groups. Stress-induced myocardial ischemia caused dyssynchronous contraction in the ischemic region, leading to a deterioration in LV synchrony. Normal myocardium had more synchronous contraction during stress. The different dyssynchrony pattern between ischemic and normal myocardium early post-stress may aid the diagnosis of coronary artery disease using {sup 201}Tl gated SPECT MPI. (orig.)

  3. Effect of siRNA silencing of inducible co-stimulatory molecule on myocardial cell hypertrophy after cardiac infarction in rats.

    Science.gov (United States)

    Wang, W M; Liu, Z; Chen, G

    2016-05-20

    As the most common cardiac disease, myocardial infarction is followed by hypertrophy of cardiac myocytes and reconstruction of ventricular structure. The up-regulation of a series of factors including metalloproteinases, inflammatory factors, and growth factors after primary infarction lead to the hypertrophy, apoptosis, necrosis, and fibroblast proliferation in cardiac muscle tissues. Recent studies have reported on the potency of small interfering RNA (siRNA) in treating cardiac diseases. We thus investigated the efficacy of inducible co-stimulatory molecule (ICOS)-specific siRNA silencing in myocardial hypertrophy in a cardiac infarction rat model. This cardiac infarction model was prepared by ligating the left anterior descending coronary artery. ICOS-siRNA treatment was administered in parallel with non-sense siRNA. After 18 days, the cross-sectional area of cardiac muscle tissues and the left ventricle weight index were measured, along with ICOS mRNA and protein expression levels, and pathological staining. Compared to those in the control groups, in myocardial infarcted rats, the application of ICOS-siRNA effectively decreased the left ventricle weight index, as well as the surface area of cardiac myocytes. Both mRNA and protein levels of ICOS were also significantly decreased. HE staining was consistent with these results. In conclusion, ICOS-targeted siRNA can effectively silence gene expression of ICOS, and provided satisfactory treatment efficacy for myocardial cell hypertrophy after infarction.

  4. Myocardial Bridging

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2016-02-01

    Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

  5. Marrubium vulgare L. methanolic extract inhibits inflammatory response and prevents cardiomyocyte fibrosis in isoproterenol-induced acute myocardial infarction in rats.

    Science.gov (United States)

    Yousefi, Keyvan; Fathiazad, Fatemeh; Soraya, Hamid; Rameshrad, Maryam; Maleki-Dizaji, Nasrin; Garjani, Alireza

    2014-01-01

    Nowadays, finding new therapeutic compounds from natural products for treatment and prevention of a variety of diseases including cardiovascular disorders is getting a great deal of attention. This approach would result in finding new drugs which are more effective and have fewer side effects than the conventional medicines. The present study was designed to investigate the anti-inflammatory effect of the methanolic extract of Marrubiumvulgare, a popular traditional medicinal herb, on isoproterenol-induced myocardial infarction (MI) in rat model. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for two consecutive days was used to induce MI. Then, histopathological changes and inflammatory markers were evaluated. Isoproterenol injection increased inflammatory response, as shown by a significant increase in peripheral neutrophil count, myocardial myeloperoxidase (MPO) activity and serum levels of creatinine kinase-MB (CK-MB) and TNF-α (pvulgare extract serum CK-MB was subsided by 55.4%, 52.2% and 69%, respectively. Also treatment with the extract (40 mg/kg) significantly reduced (pvulgare extract has strong protective effects against isoproterenol-induced myocardial infarction and it seems possible that this protection is due to its anti-inflammatory effects.

  6. Relation between exercise-induced ventricular arrhythmias and myocardial perfusion abnormalities in patients with intermediate pretest probability of coronary artery disease

    International Nuclear Information System (INIS)

    Elhendy, A.; Sozzi, F.B.; Van Domburg, R.T.; Bax, J.J.; Roelandt, J.R.T.C.

    2000-01-01

    We studied 302 patients (mean age 54±9 years, 152 men and 150 women) with intermediate pretest probability of CAD (range=0.25- 0.80, mean=0.43±0.20) by upright bicycle exercise stress test in conjunction with technetium-99m single-photon emission tomography (SPET) imaging. Exercise-induced VAs (frequent or complex premature ventricular contractions or ventricular tachycardia) occurred in 65 patients (22%). No significant difference was found between patients with and patient without VAs regarding the pretest probability of CAD (0.45±0.21 vs 0.43±0.20). Patients with exercise-induced VAs had a higher prevalence of perfusion abnormalities (52% vs 26%, P=0.002) and ischaemic electrocardiographic changes (31% vs 16%, P<0.05) compared to patients without VAs. A higher prevalence of perfusion abnormalities in patients with VAs was observed in both men (67% vs 35%, P<0.01) and women (38% vs 16%, P<0.05). However, the positive predictive value of exercise-induced VAs for the presence of myocardial perfusion abnormalities was higher in men than in women (67% vs 38%, P<0.05). The presence of abnormal myocardial perfusion was the only independent predictor of exercise-induced VAs (OR 2.2; 95% CI, 1.2-4.2) by multivariate analysis of clinical and stress test variables. It is concluded that in patients with intermediate pretest probability of CAD, exercise-induced VAs are predictive of a higher prevalence of myocardial perfusion abnormalities in both men and women. However, the positive predictive value of exercise-induced VAs for perfusion abnormalities is higher in men. Because of the underestimation of ischaemia by electrocardiographic changes, exercise-induced VAs should be interpreted as a marker of a higher probability of CAD. (orig./MG) (orig.)

  7. Endothelial dysfunction, carotid artery plaque burden, and conventional exercise-induced myocardial ischemia as predictors of coronary artery disease prognosis

    Directory of Open Access Journals (Sweden)

    Ishihara Masayuki

    2008-12-01

    Full Text Available Abstract Background While both flow-mediated vasodilation (FMD in the brachial artery (BA, which measures endothelium-dependent vasodilatation, and intima-media thickness (IMT in the carotid artery are correlated with the prognosis of coronary artery disease (CAD, it is not clear which modality is a better predictor of CAD. Furthermore, it has not been fully determined whether either of these modalities is superior to conventional ST-segment depression on exercise stress electrocardiogram (ECG as a predictor. Thus, the goal of the present study was to compare the predictive value of FMD, IMT, and stress ECG for CAD prognosis. Methods and Results A total of 103 consecutive patients (62 ± 9 years old, 79 men with clinically suspected CAD had FMD and nitroglycerin-induced dilation (NTG-D in the BA, carotid artery IMT measurement using high-resolution ultrasound, and exercise treadmill testing. The 73 CAD patients and 30 normal coronary patients were followed for 50 ± 15 months. Fifteen patients had coronary events during this period (1 cardiac death, 2 non-fatal myocardial infarctions, 3 acute heart failures, and 9 unstable anginas. On Kaplan-Meier analysis, only FMD and stress ECG were significant predictors for cardiac events. Conclusion Brachial endothelial function as reflected by FMD and conventional exercise stress testing has comparable prognostic value, whereas carotid artery plaque burden appears to be less powerful for predicting future cardiac events.

  8. Role of Extracorporeal Membrane Oxygenation in Aluminum Phosphide Poisoning-Induced Reversible Myocardial Dysfunction: A Novel Therapeutic Modality.

    Science.gov (United States)

    Mohan, Bishav; Gupta, Vivek; Ralhan, Sarju; Gupta, Dinesh; Puri, Sandeep; Wander, Gurpreet Singh; Singh, Bhupinder

    2015-11-01

    Aluminum phosphide (AlP) poisoning carries a high rate of mortality despite intensive care management, primarily because of refractory myocardial depression, resistant hypotension, and severe metabolic acidosis as well as acute respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) is a modified "heart-lung" machine to provide temporary cardiorespiratory support. We studied the novel use of ECMO in the management of a subset of patients with AlP poisoning. In this case series, seven patients with AlP poisoning suffering from severe metabolic acidosis and refractory cardiogenic shock with a reduced left ventricular ejection fraction (poisoning-induced severe metabolic acidosis and refractory cardiogenic shock may lead to a significant improvement in overall survival. Therefore, ECMO might be considered as a bridge therapy for patients with intractable cardiorespiratory failure caused by AlP poisoning who are not responding to conventional treatment. ECMO, however, also is associated with significant complication rates, which must be incorporated into the risk-benefit analysis while considering treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

    Directory of Open Access Journals (Sweden)

    Veronica Ghiglieri

    2012-01-01

    Full Text Available In Parkinson’s disease (PD, alteration of dopamine- (DA- dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID. Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

  10. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees...... that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation...

  11. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    Science.gov (United States)

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  12. Oxidative stress in immature brain following experimentally-induced seizures

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava

    2013-01-01

    Roč. 62, Suppl.1 (2013), S39-S48 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR(CZ) GA309/08/0292; GA ČR(CZ) GAP303/10/0999; GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) LL1204 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : immature rats * experimentally-induced seizures * oxidative stress * mitochondrial dysfunction * antioxidant defense Subject RIV: FH - Neurology Impact factor: 1.487, year: 2013

  13. Patterns of experimentally induced pain in pericranial muscles

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

    2006-01-01

    Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...... (VAS) and the perceived area of pain was drawn on anatomical maps. The pain areas were measured and the localization determined by a new centre-of-gravity method. The PPTs were lowest on the sternocleidomastoid muscle (anova: P ... into the masseter muscle (anova: P muscles had significantly different patterns of spread and referral of pain according to trigeminally vs...

  14. Experimental identification of pedestrian-induced lateral forces on footbridges

    DEFF Research Database (Denmark)

    Ingólfsson, Einar Thór; Georgakis, Christos; Ricciardelli, Francesco

    2011-01-01

    combinations of frequencies (0.33-1.07 Hz) and amplitudes 4.5-48 mm). The experimental campaign involved seventy-one male and female human adults and covered approximately 55 km of walking distributed between 4954 individual tests. When walking on a laterally moving surface, motion-induced forces develop also...... with the acceleration of the treadmill depends on the frequency of the movement, such that pedestrians (on average) add to the overall modal mass for low frequency motion and subtract from the overall modal mass at higher frequencies....

  15. Alignment of inducible vascular progenitor cells on a micro-bundle scaffold improves cardiac repair following myocardial infarction.

    Science.gov (United States)

    Jamaiyar, Anurag; Wan, Weiguo; Ohanyan, Vahagn; Enrick, Molly; Janota, Danielle; Cumpston, Devan; Song, Hokyung; Stevanov, Kelly; Kolz, Christopher L; Hakobyan, Tatev; Dong, Feng; Newby, Bi-Min Zhang; Chilian, William M; Yin, Liya

    2017-07-01

    Ischemic heart disease is still the leading cause of death even with the advancement of pharmaceutical therapies and surgical procedures. Early vascularization in the ischemic heart is critical for a better outcome. Although stem cell therapy has great potential for cardiovascular regeneration, the ideal cell type and delivery method of cells have not been resolved. We tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction. iVPCs partially reprogrammed from vascular endothelial cells (ECs) had potent angiogenic potential and were able to simultaneously differentiate into vascular smooth muscle cells (SMCs) and ECs in 2D culture. Under hypoxic conditions, iVPCs also secreted angiogenic cytokines such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as measured by enzyme-linked immunosorbent assay (ELISA). A longitudinal micro-scaffold made from poly(lactic-co-glycolic acid) was sufficient for the growth and delivery of iVPCs. Co-cultured ECs and SMCs aligned well on the micro-bundle scaffold similarly as in the vessels. 3D cell/polymer micro-bundles formed by iVPCs and micro-scaffolds were transplanted into the ischemic myocardium in a rat model of myocardial infarction (MI) with ligation of the left anterior descending artery. Our in vivo data showed that iVPCs on the micro-bundle scaffold had higher survival, and better retention and engraftment in the myocardium than free iVPCs. iVPCs on the micro-bundles promoted better cardiomyocyte survival than free iVPCs. Moreover, iVPCs and iVPC/polymer micro-bundles treatment improved cardiac function (ejection fraction and fractional shortening, endocardial systolic volume) measured by echocardiography, increased vessel density, and decreased infarction size [endocardial and epicardial infarct (scar) length] better than untreated controls at 8 weeks after MI

  16. Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia.

    Science.gov (United States)

    Terkelsen, Astrid J; Bach, Flemming W; Jensen, Troels S

    2008-08-01

    Complex regional pain syndrome is a painful condition of unknown etiology. Clinical and experimental observations suggest that limb immobilization may induce symptoms and signs characteristic of complex regional pain syndrome. This study examined the effect of forearm immobilization on regional sensory and autonomic functions in healthy subjects. Thermal and mechanical sensitivity, skin temperature, and vasoconstrictor responses were measured in 30 healthy subjects before and 0, 3, and 28 days after scaphoid cast immobilization. Fifteen subjects served as nonimmobilized controls. At cast removal, 27 subjects experienced pain at joint movement. Cast immobilization induced cold hyperalgesia in glabrous and hairy skin on the immobilized hand and induced significant skin temperature differences between the control and the immobilized hand at cast removal and after 3 days. Immobilization also reduced pain threshold at skin fold testing at all time points after cast removal. All measures except pain threshold at skin fold testing were normalized after 28 days. Immobilization did not affect thermal detection, heat pain, and pressure pain thresholds; resting skin perfusion; or vasoconstrictor responses induced by mental stress or deep inspirations. Four weeks of forearm immobilization caused transient changes in skin temperature, mechanosensitivity, and thermosensitivity, without alteration in the sympathetically mediated vascular tone.

  17. Immediate effects of chocolate on experimentally induced mood states.

    Science.gov (United States)

    Macht, Michael; Mueller, Jochen

    2007-11-01

    In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress.

  18. An experimental model of hemolysis-induced acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Saruc M.

    2003-01-01

    Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

  19. A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats.

    Science.gov (United States)

    Giudice, Pietro Lo; Bonomini, Mario; Arduini, Arduino

    2016-04-01

    The myocardium is largely dependent upon oxidation of fatty acids for the production of ATP. Cardiac contractile abnormalities and failure have been reported after acute emotional stress and there is evidence that catecholamines are responsible for acute stress-induced heart injury. We hypothesized that carnitine deficiency increases the risk of stress-induced heart injury. Carnitine deficiency was induced in Wistar rats by adding 20 mmol/L of sodium pivalate to drinking water (P). Controls (C) received equimolar sodium bicarbonate and a third group (P + Cn) received pivalate along with 40 mmol/L carnitine. After 15 days, 6 rats/group were used to evaluate function of isolated hearts under infusion of 0.1 μM isoproterenol and 20 rats/group were submitted to a single subcutaneous administration of 50 mg/kg isoproterenol. Isoproterenol infusion in C markedly increased the heart rate, left ventricular (LV) systolic pressure and coronary flow rate. In P rats, isoproterenol increased the heart rate and LV systolic pressure but these increases were not paralleled by a rise in the coronary flow rate and LV diastolic pressure progressively increased. Subcutaneous isoproterenol induced 15 % mortality rate in C and 50 % in P (p deficiency exposes the heart to a greater risk of injury when sympathetic nerve activity is greatly stimulated, for example during emotional, mental or physical stress.

  20. Green tea polyphenols avert chronic inflammation-induced myocardial fibrosis of female rats

    Science.gov (United States)

    Objective: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. Treatments: Fo...

  1. Transauricular embolization of the rabbit coronary artery for experimental myocardial infarction: comparison of a minimally invasive closed-chest model with open-chest surgery

    Directory of Open Access Journals (Sweden)

    Katsanos Konstantinos

    2012-02-01

    Full Text Available Abstract Introduction To date, most animal studies of myocardial ischemia have used open-chest models with direct surgical coronary artery ligation. We aimed to develop a novel, percutaneous, minimally-invasive, closed-chest model of experimental myocardial infarction (EMI in the New Zealand White rabbit and compare it with the standard open-chest surgical model in order to minimize local and systemic side-effects of major surgery. Methods New Zealand White rabbits were handled in conformity with the "Guide for the Care and Use of Laboratory Animals" and underwent EMI under intravenous anesthesia. Group A underwent EMI with an open-chest method involving surgical tracheostomy, a mini median sternotomy incision and left anterior descending (LAD coronary artery ligation with a plain suture, whereas Group B underwent EMI with a closed-chest method involving fluoroscopy-guided percutaneous transauricular intra-arterial access, superselective LAD catheterization and distal coronary embolization with a micro-coil. Electrocardiography (ECG, cardiac enzymes and transcatheter left ventricular end-diastolic pressure (LVEDP measurements were recorded. Surviving animals were euthanized after 4 weeks and the hearts were harvested for Hematoxylin-eosin and Masson-trichrome staining. Results In total, 38 subjects underwent EMI with a surgical (n = 17 or endovascular (n = 21 approach. ST-segment elevation (1.90 ± 0.71 mm occurred sharply after surgical LAD ligation compared to progressive ST elevation (2.01 ± 0.84 mm;p = 0.68 within 15-20 min after LAD micro-coil embolization. Increase of troponin and other cardiac enzymes, abnormal ischemic Q waves and LVEDP changes were recorded in both groups without any significant differences (p > 0.05. Infarct area was similar in both models (0.86 ± 0.35 cm in the surgical group vs. 0.92 ± 0.54 cm in the percutaneous group;p = 0.68. Conclusion The proposed model of transauricular coronary coil embolization avoids

  2. Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

    Science.gov (United States)

    Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

    2016-04-15

    We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. Copyright © 2016 the American Physiological Society.

  3. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

    Science.gov (United States)

    Coloma, Preciosa M; Schuemie, Martijn J; Trifirò, Gianluca; Furlong, Laura; van Mulligen, Erik; Bauer-Mehren, Anna; Avillach, Paul; Kors, Jan; Sanz, Ferran; Mestres, Jordi; Oliveira, José Luis; Boyer, Scott; Helgee, Ernst Ahlberg; Molokhia, Mariam; Matthews, Justin; Prieto-Merino, David; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; van der Lei, Johan; Sturkenboom, Miriam

    2013-01-01

    Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings. To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects'): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association

  4. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

    Directory of Open Access Journals (Sweden)

    Preciosa M Coloma

    Full Text Available Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings.To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI from a large international healthcare data network.Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible.Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects': azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate.Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out.A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical

  5. Experimental neurocysticercosis: absence of IL-4 induces lower encephalitis

    Directory of Open Access Journals (Sweden)

    Hidelberto Matos Silva

    Full Text Available ABSTRACT Neurocysticercosis (NCC is the most severe clinical manifestation of cysticercosis. One of the factors responsible for its symptomatology is the host inflammatory response. Therefore the influence of interleukin 4 (IL-4 on the induction of encephalitis in experimental NCC was evaluated. Methods BALB/c (WT and BALB/c (IL-4-KO mice were inoculated intracranially with Taenia crassiceps cysticerci and euthanized at 7, 30, 60 and 90 days later, the encephala removed and histopathologically analyzed. Results The absence of IL-4 induced greater parasitism. In the initial phase of the infection, IL-4-KO showed a lower intensity in the inflammatory infiltration of polimorphonuclear cells in the host-parasite interface and intra-parenquimatous edema. The IL-4-KO animals, in the late phase of the infection, showed lower intensity of ventriculomegaly, encephalitis, and meningitis, and greater survival of the parasites in comparison with the WT animals. Conclusion The absence of IL-4 induced lower inflammatory infiltration, ventriculomegaly and perivasculitis in experimental NCC.

  6. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  7. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction

    NARCIS (Netherlands)

    González-Santamaría, J.; Villalba, M.; Busnadiego, O.; López-Olañeta, M.M.; Sandoval, P.; Snabel, J.; López-Cabrera, M.; Erler, J.T.; Hanemaaijer, R.; Lara-Pezzi, E.; Rodríguez-Pascual, F.

    2016-01-01

    Aims After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular

  8. The influence of experimentally induced pain on shoulder muscle activity.

    Science.gov (United States)

    Diederichsen, Louise Pyndt; Winther, Annika; Dyhre-Poulsen, Poul; Krogsgaard, Michael R; Nørregaard, Jesper

    2009-04-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0 degrees -105 degrees) at a speed of approximately 120 degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load

  9. Past Pain Experience and Experimentally induced Pain Perception.

    Science.gov (United States)

    Paquet, Aude; Plansont, Brigitte; Labrunie, Anaïs; Malauzat, Dominique; Girard, Murielle

    2017-12-01

    Many intercurrent factors may be involved in the modulation of the pain message and its expression, such as the previous experience of pain built along the life. In this study, we aimed to determine whether susceptibility to experimentally induced pain is differentially influenced by the individual previous painful experience in subjects with schizophrenia (SC) major depression (MD), and controls (C). The SC (30), MD (32) and C (30) groups participated in experimental pain tests (application of pressure and induction of ischemia) after a semi-structured interview to make an inventory of the previous painful experiences, and the evaluation of anxiety either with autonomic (heart rate, blood pressure) or psychological (Hospital Anxiety Depression scale HAD) measures, and catastrophism. The reported pain intensities, severities, duration, of the previous pain events, and the number of previous painful events were equivalent in the three groups, except for the number of painful events experimented before the last six months which was lower in the MD group. Experimental pain sensitivity was influenced by the diagnosis, the HAD scores or the number and intensities of previous lived painful events. The lack of a past experience of pain was comparable for the different groups, suggesting that psychiatric disorders do not affect the experience of pain associated with daily life or past events. For each subject, the reported previous experience of pain influences the present feeling of pain.

  10. The Novel Extracellular Cyclophilin A (CyPA - Inhibitor MM284 Reduces Myocardial Inflammation and Remodeling in a Mouse Model of Troponin I -Induced Myocarditis.

    Directory of Open Access Journals (Sweden)

    David Heinzmann

    Full Text Available Cyclophilins are a group of highly conserved cytosolic enzymes that have a peptidylprolyl cis/trans isomerase activity. Cyclophilin A (CyPA can be secreted in the extracellular space by inflammatory cells and upon cell death. The presence of CyPA in patients with non-ischemic cardiomyopathy is associated with poor clinical prognosis. Here, we investigated the inhibition of extracellular CyPA in a mouse model of troponin I-induced autoimmune myocarditis using the strictly extracellular CyPA-inhibitor MM284. Since A/J mice develop severe inflammation and fibrosis after immunization with murine cardiac troponin I (mcTn I, we used this model to analyze the effects of an extracellular CyPA inhibition. As extracellular CyPA-inhibitor we used the recently described CsA-derivate MM284. In vitro studies confirmed that MM284 inhibits CyPA-induced monocytic migration and adhesion. A/J mice immunized with mcTnI were treated with MM284 or vehicle every second day. After 28 days, we found a considerable reduction of myocardial injury and fibrosis. Further analysis revealed a reduced myocardial presence of T-cells and macrophages compared to control treated animals. Whereas MMP-9 expression was reduced significantly by MM284, we observed no significant reduction of inflammatory cytokines such as IL-6 or TNFα. Extracellular CyPA plays an important role in autoimmune myocarditis for myocardial damage and fibrosis. Our data suggest a new pharmacological approach for the treatment of myocardial inflammation and reduction of cardiac fibrosis by inhibition of extracellular CyPA.

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

    NARCIS (Netherlands)

    Smeding, Lonneke; Plotz, Frans B.; Lamberts, Regis R.; van der Laarse, Willem J.; Kneyber, Martin C. J.; Groeneveld, A. B. Johan

    2012-01-01

    Background: Injurious mechanical ventilation (MV) may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We

  12. Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II

    Directory of Open Access Journals (Sweden)

    Ning-Ping Wang

    2017-05-01

    Full Text Available Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.

  13. Resveratrol attenuated hydrogen peroxide-induced myocardial apoptosis by autophagic flux

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    Chih-Yang Huang

    2016-05-01

    Full Text Available Background: Resveratrol is a Sirt-1-specific activator, which also exerts cardioprotective effects that regulate redox signalling during oxidative stress and autophagy during cardiovascular disease (CVD. Objective: This study investigated the protective effects of resveratrol against hydrogen peroxide-induced damage in cardiomyocytes. Design: In this article, hydrogen peroxide-induced autophagy and apoptosis in H9c2 cardiomyoblasts were studied at an increasing concentration from 0 to 100 µM. Results: Resveratrol pretreatment with concentrations of 10, 20, and 50 µM inhibits autophagic apoptosis by increasing p-Akt and Bcl-2 protein levels in H9c2 cells. Interestingly, resveratrol treatment activates the Beclin-1, LC3, p62, and the lysosome-associated protein LAMP2a within 24 h of administration. Conclusions: These results suggest that resveratrol-regulated autophagy may play a role in degrading damaged organelles in H9c2 cells rather than causing apoptosis, and this may be a possible mechanism by which resveratrol protects the heart during CVD.

  14. Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

    Directory of Open Access Journals (Sweden)

    Giono Silvia

    2002-06-01

    Full Text Available Abstract Background Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints. Methods P-140 and PG-18 strains were each injected in the knee joints of 14 rabbits in order to evaluate and compare their arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order to test the ability of the bacteria to reach the joints and induce arthritis. Results M. fermentans produced an acute arthritis in rabbits. Joint swelling appeared first in rabbits injected with P-140, which caused a more severe arthritis than PG-18. Both strains were able to migrate to the uninoculated knee joints and they were detected viable in the joints all along the duration of the experiment. Changes in the synovial tissue were more severe by the end of the experiment and characterized by the infiltration of neutrophils and substitution of adipose tissue by connective tissue. Rabbits intracheally injected with P-140 showed induced arthritis and the bacteria could be isolated from lungs, blood, heart, kidney, spleen, brain and joints. Conclusion M. fermentans induced arthritis regardless of the inoculation route. These findings may help explain why mycoplasmas are commonly isolated from the joints of rheumatic patients.

  15. Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

    Directory of Open Access Journals (Sweden)

    B.B. Matsubara

    2010-05-01

    Full Text Available It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1% NaCl in the drinking water, N = 9; ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12; ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10. All results were compared with those of age-matched, untreated rats (CTL group, N = 10. After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg was significantly elevated (P < 0.05 in ALDO (180 ± 20 and ALDOF (168 ± 13 compared to CTL (123 ± 12 and CNEP (134 ± 13. Heart damage (lesion scores - median and interquartile range was 7.0 (5.5-8.0 in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0. Also, left ventricular collagen volume fraction (% in ALDOF (2.9 ± 0.5 was similar to CTL (2.9 ± 0.5 and CNEP (3.4 ± 0.4 and decreased compared to ALDO (5.1 ± 1.6. Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0 was significantly decreased compared to ALDO (7.5; 4.0-10.5, although higher than CTL (null score. Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.

  16. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  17. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper......-105A degrees) at a speed of approximately 120A degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder...... trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows...

  18. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation...... in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load on the painful structures Udgivelsesdato: 2009/4...

  19. MRI of myocardial perfusion.

    Science.gov (United States)

    Jerosch-Herold, Michael; Muehling, Olaf; Wilke, Norbert

    2006-02-01

    An overwhelming number of myocardial perfusion studies are done by nuclear isotope imaging. Magnetic resonance imaging during the first pass of an injected, contrast bolus has some significant advantages for detection of blood flow deficits, namely higher spatial resolution, absence of ionizing radiation, and speed of the test. Previous clinical studies have demonstrated that excellent sensitivity and specificity can be achieved with MR myocardial perfusion imaging for detecting coronary artery disease, and assessment of patients with acute chest pain. Furthermore, an absolute quantification of myocardial blood flow is feasible, as was demonstrated by comparison of MR perfusion imaging, to measurements with isotope labeled microspheres in experimental models. An integrated assessment of perfusion, function, and viability, is thus feasible by MRI to answer important clinical challenges such as the identification of stunned or hibernating, but viable myocardium.

  20. Cardiac fibrosis in mice expressing an inducible myocardial-specific Cre driver

    Directory of Open Access Journals (Sweden)

    Jonas Lexow

    2013-11-01

    Tamoxifen-inducible Cre-mediated manipulation of animal genomes has achieved wide acceptance over the last decade, with numerous important studies heavily relying on this technique. Recently, a number of groups have reported transient complications of using this protocol in the heart. In the present study we observed a previously unreported focal fibrosis and depressed left-ventricular function in tamoxifen-treated αMHC-MerCreMer-positive animals in a Tβ4shRNAflox × αMHC-MerCreMer cross at 6–7 weeks following standard tamoxifen treatment, regardless of the presence of the floxed transgene. The phenotype was reproduced by treating mice from the original αMHC-MerCreMer strain with tamoxifen. In the acute phase after tamoxifen treatment, cell infiltration into the myocardium was accompanied by increased expression of pro-inflammatory cytokines (IL-1β, IL-6, TNFα, IFNγ, Ccl2 and markers of hypertrophy (ANF, BNP, Col3a1. These observations highlight the requirement for including tamoxifen-treated MerCreMer littermate controls to avert misinterpretation of conditional mutant phenotypes. A survey of the field as well as the protocols presented here suggests that controlling the parameters of tamoxifen delivery is important in avoiding the chronic MerCreMer-mediated cardiac phenotype reported here.

  1. Ionizing radiation-induced cancers. Experimental and clinical data

    International Nuclear Information System (INIS)

    Joveniaux, Alain.

    1978-03-01

    This work attempts to give an idea of radiocarcinogenesis, both experimental and clinical. Experimentally the possibility of radio-induced cancer formation has considerable doctrinal importance since it proves without question the carcinogenetic effect of radiations, and also yields basis information on the essential constants implicated in its occurrence: need for a latency time varying with the animal species and technique used, but quite long in relation to the specific lifetime of each species; importance of a massive irradiation, more conducive to cancerisation as long as it produces no necroses liable to stop the formation of any subsequent neoplasia; finally, rarity of is occurrence. Clinically although the cause and effect relationship between treatment and cancer is sometimes difficult to establish categorically, the fact is that hundreds of particularly disturbing observations remain and from their number often emerges under well-defined circumstances, an undeniable clinical certainty. Most importantly these observation fix the criteria necessary for the possibility of a radioinduced cancer to arise, i.e: the notion of a prior irradiation; the appearance of a cancer in the irradiation area; serious tissue damage in relation with an excessive radiation dose; a long latency period between irradition and appearance of the cancer [fr

  2. Inflammation-induced preterm lung maturation: lessons from animal experimentation.

    Science.gov (United States)

    Moss, Timothy J M; Westover, Alana J

    2017-06-01

    Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

  3. Foraminiferal survival after long term experimentally induced anoxia

    Science.gov (United States)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-06-01

    Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

  4. : Myocardial Perfusion

    OpenAIRE

    Dacher, Jean-Nicolas; Lefebvre, V.; Dubourg, Bernard; Deux, Jean-François; Caudron, Jérôme

    2013-01-01

    International audience; The analysis of myocardial perfusion is a key step in the cardiac MRI examination. In routine work, this exploration carried out at rest is based on the qualitative first pass study of gadolinium with an ECG-triggered saturation recovery bFFE sequence. In view of recent knowledge, the analysis of the myocardial perfusion under vasodilator stress may be carried out by scintigraphy or MRI, the latter benefiting from the absence of exposure to ionizing rays and a lower co...

  5. Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study.

    Science.gov (United States)

    Chagoya de Sánchez, V; Hernández-Muñoz, R; López-Barrera, F; Yañez, L; Vidrio, S; Suárez, J; Cota-Garza, M D; Aranda-Fraustro, A; Cruz, D

    1997-12-01

    Acute myocardial infarction is the second cause of mortality in most countries, therefore, it is important to know the evolution and sequence of the physiological and biochemical changes involved in this pathology. This study attempts to integrate these changes and to correlate them in a long-term model (96 h) of isoproterenol-induced myocardial cell damage in the rat. We achieved an infarct-like damage in the apex region of the left ventricle, occurring 12-24 h after isoproterenol administration. The lesion was defined by histological criteria, continuous telemetric ECG recordings, and the increase in serum marker enzymes, specific for myocardial damage. A distinction is made among preinfarction, infarction, and postinfarction. Three minutes after drug administration, there was a 60% increase in heart rate and a lowering of blood pressure, resulting possibly in a functional ischemia. Ultrastructural changes and mitochondrial swelling were evident from the first hour of treatment, but functional alterations in isolated mitochondria, such as decreases in oxygen consumption, respiratory quotient, ATP synthesis, and membrane potential, were noticed only 6 h after drug administration and lasted until 72 h later. Mitochondrial proteins decreased after 3 h of treatment, reaching almost a 50% diminution, which was maintained during the whole study. An energy imbalance, reflected by a decrease in energy charge and in the creatine phosphate/creatine ratio, was observed after 30 min of treatment; however, ATP and total adenine nucleotides diminished clearly only after 3 h of treatment. All these alterations reached a maximum at the onset of infarction and were accompanied by damage to the myocardial function, drastically decreasing left ventricular pressure and shortening the atrioventricular interval. During postinfarction, a partial recovery of energy charge, creatine phosphate/creatine ratio, membrane potential, and myocardial function occurred, but not of mitochondrial

  6. miR-34a Modulates Angiotensin II-Induced Myocardial Hypertrophy by Direct Inhibition of ATG9A Expression and Autophagic Activity

    Science.gov (United States)

    Huang, He; Ye, Jing; Pan, Wei; Zhong, Yun; Cheng, Chuanfang; You, Xiangyu; Liu, Benrong; Xiong, Longgen; Liu, Shiming

    2014-01-01

    Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. PMID:24728149

  7. Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-βl and Smad2/3 pathways in high-fat diet-induced obesity rat model.

    Science.gov (United States)

    Hong, Seul-Ki; Choo, Eun-Ho; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

    2017-11-01

    Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-β1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-β1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-β1-induced collagen production and TGF-β1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-β1 and Smad2/3 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. E2/ER β Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Kuan-Ho Lin

    2017-04-01

    Full Text Available Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2, for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs. In addition, protein phosphatase such as protein phosphatase 1 (PP1 and calcineurin (PP2B are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

  9. Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model.

    Science.gov (United States)

    Cetin, Bulent; Yılmaz, Guldal Esendagli; Armagan, Berkan; Afsar, Baris; Demirci, Umut; Gulbahar, Ozlem; Gumusay, Ozge; Bilgetekin, Irem; Ozet, Ahmet; Uner, Aytug

    2018-01-01

    Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity. © 2018 S. Karger AG, Basel.

  10. Pathogenesis of rhinitis in rats with experimentally induced hypothyroidism.

    Science.gov (United States)

    Eyigor, Hulya; Basak, Sema; Kozaci, Didem; Culhaci, Nil; Dost, Turhan; Ulutas, Pinar

    2012-01-01

    Hypothyroidism is accepted as one of the hormonal factors leading to non-allergic rhinitis. Nasal obstruction and runny nose due to an increase in submucosal connective tissue and mucous gland hypertrophy are the prominent symptoms in hypothyroidism-induced rhinitis at humans. The aim of this study was to analyze the biochemical and histopathological changes in the nasal mucosa of the rats with thyroidectomy-induced hypothyroidism and to compare them with those of a control group. A total of 60 adult male Wistar Albino rats were included in the study. The rats constituting the test and the control groups were randomly divided into 3 subgroups (T1-3 and C 1-3). While the rats in the test group underwent thyroidectomy, in the control group the incision was sutured without any interventions after exposure of thyroid tissues of the rats. The nasal and paranasal sinus regions of all the rats were carefully dissected and tissue samples were obtained for pathological examinations. In the rats in T1, T2, and T3, the decrease in serum glucuronic acid levels before and after thyroidectomy was statistically significant (p = 0.001, p = 0.003, and p = 0.002, respectively). The difference between the test and the control groups was statistically significant in terms of inflammation at the end of 12 weeks (p = 0.002). An increase in acid mucopolysaccharidase production due to TSH has been suggested to cause congestion in tissues. Although our study supports the data in the literature up to date, we consider that further clinical and experimental studies are necessary for this verification.

  11. Contrast-induced acute kidney injury and mortality in ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

    Science.gov (United States)

    Silvain, Johanne; Nguyen, Lee S; Spagnoli, Vincent; Kerneis, Mathieu; Guedeney, Paul; Vignolles, Nicolas; Cosker, Kristel; Barthelemy, Olivier; Le Feuvre, Claude; Helft, Gérard; Collet, Jean-Philippe; Montalescot, Gilles

    2017-11-01

    Contrast-induced acute kidney injury (CI-AKI) is a common and potentially severe complication in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). There is no consensus on the best definition of CI-AKI to identify patients at risk of haemodialysis or death. The objective of this study was to assess the association of CI-AKI, using four definitions, on inhospital mortality, mortality or haemodialysis requirement over 1-year follow-up, in patients with STEMI treated with pPCI. In this prospective, observational study, all patients with STEMI referred for pPCI were included. We identified independent variables associated with CI-AKI and mortality. We included 1114 consecutive patients with STEMI treated by pPCI. CI-AKI occurred in 18.3%, 12.2%, 15.6% and 10.5% of patients according to the CIN, Acute Kidney Injury Network (AKIN), Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) Modification of Diet in Renal Disease(MDRD) and RIFLE Chronic Kidney Disease - Epidemiology Collaboration(CKD-EPI) definitions, respectively. The RIFLE (CKD-EPI) definition was the most discriminant definition to identify patients at higher risk of inhospital mortality (27.1% vs 4.0%; adjusted OR 2.7(95% CI 1.4 to 5.1), p=0.003), 1-year mortality (27.4% vs 6.6%; adjusted OR 2.8(95% CI 1.5 to 5.3), p=0.002) and haemodialysis requirement at 1-year follow-up (15.6% vs 2.7%; adjusted OR 6.7(95% CI 3.3 to 13.6), p=0.001). Haemodynamic instability, cardiac arrest, preexisting renal failure, elderly age and a high contrast media volume were independently associated with 1-year mortality. Of interest, contrast-media volume was not correlated to increase of creatininaemia (r=0.06) or decrease in estimated glomerular filtration rate (r=0.05) after percutaneous coronary intervention in our population. CI-AKI is a frequent and serious complication of STEMI treated by pPCI. The RIFLE definition is the

  12. Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related

    Czech Academy of Sciences Publication Activity Database

    Janega, P.; Kojšová, S.; Jendeková, L.; Babál, P.; Pecháňová, Olga

    2007-01-01

    Roč. 56, č. 6 (2007), s. 825-828 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : indapamide * myocardial fibrosis * genetic hypertension Subject RIV: ED - Physiology Impact factor: 1.505, year: 2007

  13. Calcium channel blockade limits cardiac remodeling and improves cardiac function in myocardial infarction-induced heart failure in rats

    NARCIS (Netherlands)

    Sandmann, S.; Claas, R.; Cleutjens, J. P.; Daemen, M. J.; Unger, T.

    2001-01-01

    Calcium channel antagonists (CCAs) have been proposed to prevent cardiac events after myocardial infarction (MI). However, unwanted effects, such as negative inotropy, limit their use in many cases. The aim of this study was to compare the effects of long-term treatment with the CCAs, mibefradil,

  14. Dynamic myocardial perfusion in a porcine balloon-induced ischemia model using a prototype spectral detector CT

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Fares, Anas; Levi, Jacob; Wu, Hao; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR < 0.7), and we found that flow

  15. The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

    Science.gov (United States)

    Malatesta, M.

    The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and

  16. Myocardial scintigraphy

    International Nuclear Information System (INIS)

    Bunko, Hisashi; Hisada, Kinichi

    1982-01-01

    Among the various methods of image diagnosis of the cardiovascular disorder, nuclear cardiology provides noninvasive means for evaluation of myocardial perfusion as well as morphological and functional informations. In this article, clinical application and image diagnosis of myocardial scintigraphy including Tl-201 myocardial perfusion scintigraphy, single photon emission computed tomography with Tl-201, acute myocardial infarction scintigraphy with Tc-99m-pyrophosphate and Ga-67 imaging of the heart, were discussed. Multiplanar imaging of the heart with Tl-201 after stress and at redistribution was the accepted method for detection and evaluation of the ischemic heart disease. Although it achieved high sensitivity and specificity for ischemic heart disease, detection of the small ischemia and quantation of the regional Tl-201 accumulation were difficult with conventional multiplanar imaging. Application of emission computed tomography improved detectability and quantitativity of the ischemia. However, 7-pinhole tomography did not increase the diagnostic accuracy significantly. It had limited clinical applicability due to poor quantitativity in spite of improved image contrast and its tomographic nature. Advantage and limitation of these tomographic imaging and multiplanar imaging were discussed. Problems and prognostic significance of pyrophosphate imaging of the acute myocardial infarction were also discussed. Visualization of the heart with Ga-67 was helpful for identification of the tumor or inflammation of the heart as well as evaluation of the effect of the therapy. (author)

  17. Aqueous extract from leaf of Artocarpus altilis provides cardio-protection from isoproterenol induced myocardial damage in rats: Negative chronotropic and inotropic effects.

    Science.gov (United States)

    Nwokocha, Chukwuemeka; Palacios, Javier; Simirgiotis, Mario J; Thomas, Jemesha; Nwokocha, Magdalene; Young, Lauriann; Thompson, Rory; Cifuentes, Fredi; Paredes, Adrian; Delgoda, Rupika

    2017-05-05

    The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats. Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-h period. Blood pressure readings were taken before and after the administering of ISO using the tail cuff method. ECG was performed on anaesthetized rats. Cardiac contractility was measured in isolated right atrial muscles. Assessment of myocardial infarct (MI) size, heart/body weight ratio, biochemical, hematological and histo-morphological parameters were conducted at the end of seven days. An aqueous extract from leaves of A. altilis was analyzed for organic compounds using UHPLC mass spectrometry. ISO induced myocardial damage through an elevation of the heart rate (HR), infarct size and ECG distortions. Treatment with AA significantly (p˂0.05) reduced heart/body weight ratio (49%), MI (96%), HR (27%), sympathovagal imbalance (36%) and serum cardiac biomarkers (AST, LDH, HDL, triglycerides and CCK) caused by ISO. AA decreased the beat frequency of isolated right atrium (11%) cause by ISO, an action similar to propranolol (beta-adrenergic antagonist; 20%), but showed no significant changes in the QTc intervals of the ECG (suggesting no cardio-toxic drug-herb interactions), Thirty nine compounds were detected using high resolution LC-MS analysis (HPLC-Orbitrap-APCI-MS) in the extract. Pure compounds, as gallic acid and rutin, presented a higher negative chronotropic effect, similar to propranolol. Oral administration of aqueous extract of Artocarpus artilis has cardio-protective functions in

  18. Myocardial scintigraphy in acute myocardial infarction

    International Nuclear Information System (INIS)

    Faerestrand, S.

    1984-01-01

    The sensitivity and specificity of 99m Tc-PYP myocardial scintigraphy for detecting an acute myocardial infarction were studied in 39 patients hospitalized because of central chest pain. One myocardial scintigraphic examination was done in each patient between the first and sixth day after the chest pain had started. Twenty-two patients had a myocardial infarction based on history, ECG and enzym values and myocardial scintigraphy was positive in twenty of these. Three patients with left bundle branch block and myocardial infarction all had a positive myocardial scintigram and the one patient with negative ECG and myocardial infarction also had a positive myocardial scintigram. The sensitivity is 91% and the specificity is 91.7% for 99m Tc-PYP myocardial scintigraphy in the detection of acute myocardial infarction. No complications were seen. (Auth.)

  19. Analysis of changes in sagging type ST-T segment induced by exercise. Assessment of regional myocardial blood flow using quantitative 13NH3 positron emission tomography

    International Nuclear Information System (INIS)

    Watanabe, Takuya; Akutsu, Yasushi; Okazaki, Osamu

    1995-01-01

    Regional myocardial blood flow (RMBF) associated with exercise-induced ST depression was assessed using 13 NH 3 positron emission tomography (PET) to determine the significance of horizontal and sagging type ST segments. The subjects were 25 patients with angina pectoris, 25 patients with myocardial infarction, and 5 healthy male volunteers. Eleven regions of interests (ROI) were prepared to calculate RMBF. ST segments were unchanged in 27 patients (Group A) and were depressed in 23 patients (Group B). A 10% increase in RMBF was significantly observed in Group A (74.1%) than Group B (34.8%). In Group B, ST depression was divided into horizontal type (8 patients) and sagging type (15 patients). According to the type of ST depression, RMBF was increased by 10% or more in 50% (4/8) for horizontal type and in 26.7% (4/15) for sagging type. These findings suggested that unfavorable increase in RMBF in stenosiss-related coronary vessels may contribute to the development of ST depression induced by exercise. A constant increase in RMBF in all ROIs, including those with unfavorable RMBF increase, may be involved in the occurrence of horizontal type ST depression; sagging type ST depression may, however, occur by an increased difference in blood flow between unfavorable and favorable RMBF. (N.K.)

  20. Low-dose dynamic myocardial perfusion CT image reconstruction using pre-contrast normal-dose CT scan induced structure tensor total variation regularization

    Science.gov (United States)

    Gong, Changfei; Han, Ce; Gan, Guanghui; Deng, Zhenxiang; Zhou, Yongqiang; Yi, Jinling; Zheng, Xiaomin; Xie, Congying; Jin, Xiance

    2017-04-01

    Dynamic myocardial perfusion CT (DMP-CT) imaging provides quantitative functional information for diagnosis and risk stratification of coronary artery disease by calculating myocardial perfusion hemodynamic parameter (MPHP) maps. However, the level of radiation delivered by dynamic sequential scan protocol can be potentially high. The purpose of this work is to develop a pre-contrast normal-dose scan induced structure tensor total variation regularization based on the penalized weighted least-squares (PWLS) criteria to improve the image quality of DMP-CT with a low-mAs CT acquisition. For simplicity, the present approach was termed as ‘PWLS-ndiSTV’. Specifically, the ndiSTV regularization takes into account the spatial-temporal structure information of DMP-CT data and further exploits the higher order derivatives of the objective images to enhance denoising performance. Subsequently, an effective optimization algorithm based on the split-Bregman approach was adopted to minimize the associative objective function. Evaluations with modified dynamic XCAT phantom and preclinical porcine datasets have demonstrated that the proposed PWLS-ndiSTV approach can achieve promising gains over other existing approaches in terms of noise-induced artifacts mitigation, edge details preservation, and accurate MPHP maps calculation.

  1. Experimental glomerulonephritis induced by hydrocarbon exposure: A systematic review

    Directory of Open Access Journals (Sweden)

    Ravnskov Uffe

    2005-12-01

    Full Text Available Abstract Background Much epidemiological evidence suggests that hydrocarbon exposure may induce glomerulonephritis and worsen its course in many patients. The mechanisms are unknown, however, no specific microscopic pattern has been identified, and it has also been argued that hydrocarbon exposure causes tubular damage mainly. Studying experimental animals may best answer these questions, and as no systematic review of glomerulonephritis produced experimentally by hydrocarbon exposure has been performed previously, I found it relevant to search for and analyse such studies. Methods Animal experiments having mimicked human glomerulonephritis by hydrocarbon exposure were sought on Medline and Toxnet Results Twenty-six experiments using thirteen different hydrocarbons were identified. Several human subtypes were observed including IgA nephritis, mesangial, proliferative and extracapillary glomerulonephritis, focal and focal-segmental sclerosis, minimal change nephropathy, anti-GBM and anti-TBM nephritis, and glomerulonephritis associated with peiarteritis nodosa. Glomerular proteinuria was seen in 10/12 experiments that included urine analyses, and renal failure in 5/8 experiments that included measurements of glomerular function. All experiments resulted in various degrees of tubular damage as well. In most studies, where the animals were examined at different times during or after the exposure, the renal microscopic and functional changes were seen immediately, whereas deposits of complement and immunoglobulins appeared late in the course, if at all. Conclusion These experiments are in accord with epidemiological evidence that hydrocarbon exposure may cause glomerulonephritis and worsen renal function. Probable mechanisms include an induction of autologous antibodies and a disturbance of normal immunological functions. Also, tubular damage may increase postglomerular resistance, resulting in a glomerular deposition of macromolecules. In most

  2. TENS attenuates repetition-induced summation of activity-related pain following experimentally induced muscle soreness.

    Science.gov (United States)

    Mankovsky-Arnold, Tsipora; Wideman, Timothy H; Larivière, Christian; Sullivan, Michael J L

    2013-11-01

    This study sought to determine whether repetition-induced summation of activity-related pain (RISP) could be demonstrated in healthy individuals in response to experimentally induced musculoskeletal pain. This study also assessed the effects of transcutaneous electrical nerve stimulation on RISP. The relation between the index of RISP and psychological factors such as catastrophizing and fear of pain was also explored. The sample consisted of 56 healthy (35 women, 21 men) participants who underwent 2 testing sessions, separated by 24 hours. In the first session, musculoskeletal pain was induced with a delayed-onset muscle soreness protocol. During the second session, participants were randomly assigned to the transcutaneous electrical nerve stimulation or placebo condition and were asked to rate their pain as they lifted a series of 18 weighted canisters. An index of RISP was derived as the change in pain ratings across repeated lifts. Approximately 25% of participants showed evidence of RISP. Results also revealed that transcutaneous electrical nerve stimulation attenuated the RISP effect. Psychological measures (fear of pain, catastrophizing) were not significantly correlated with the index of RISP, but the index of RISP was significantly correlated with a measure of physical tolerance. Discussion addresses the clinical implications of the findings as well as the potential mechanisms underlying RISP. This study showed that RISP could be demonstrated in healthy individuals in response to experimentally induced musculoskeletal pain with delayed-onset muscle soreness. Transcutaneous electrical nerve stimulation led to a significant reduction in RISP. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Anticoccidial effect of mananoligosacharide against experimentally induced coccidiosis in broiler.

    Science.gov (United States)

    Chand, Naila; Faheem, Hassan; Khan, Rifat Ullah; Qureshi, Muhammad Subhan; Alhidary, Ibrahim A; Abudabos, Alaeldein M

    2016-07-01

    The aim of this study was to find the effect of mananoligosacharide (MOS) in comparison with amprolium hydrochloride on performance and integrity of gut in experimentally induced coccidiosis in broiler. A total of 300, day-old male broiler chickens (Ross 308) was randomly allocated to four treatments. Each group was further divided into five replicates of 15 birds each. Group A was kept as control; group B was contaminated with Eimeria tenella, while groups C and D were infected with E. tenella and treated with MOS (0.8 g/kg feed) and anticoccidial drug, amprolium hydrochloride (12 g/100 l water), respectively. The results showed that weight gain, feed intake, and feed conversion ratio (FCR) were significantly higher (P coccidiosis during 5th, 7th, 10th, and 12th day post infection (dpi). Furthermore, the OPG was significantly lower (P < 0.05) in infected groups treated with MOS and amprolium at the studied periods (5, 7, and 10 dpi). At 12 dpi, the infected group treated with MOS showed significantly lower OPG compared to the other groups suggesting the effectiveness of MOS in comparison to amprolium. The result of pinpoint hemorrhages, thickness of cecal wall, bloody fecal contents, and mucoid contents in the cecum were significant highly (P < 0.05) in birds fed with infected oocytes. It was also noted that the differences were not significant in these parameters between amprolium and MOS-treated birds showing the effectiveness of the prebiotic agent. It was concluded from the results of the present study that MOS improved growth performance and reversed the lesions of E. tenella.

  4. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  5. Myocardial uptake and clearance of thallium-201 in normal subjects: comparison of dipyridamole-induced hyperemia with exercise stress

    International Nuclear Information System (INIS)

    Ruddy, T.D.; Gill, J.B.; Finkelstein, D.M.; Strauss, H.W.; McKusick, K.A.; Okada, R.D.; Boucher, C.A.

    1987-01-01

    Thallium-201 uptake and clearance after dipyridamole infusion may differ from that after exercise stress because the hemodynamic effects of these two interventions are different. In this study of normal volunteers, thallium kinetics after dipyridamole (n = 13) were determined from three serial image sets (early, intermediate and delayed) and from serial blood samples and compared with thallium kinetics after exercise (n = 15). Absolute myocardial thallium uptake was greater after dipyridamole compared with exercise (p less than 0.0001), although the relative myocardial distribution was similar. The myocardial clearance (%/h) of thallium was slower after dipyridamole than it was after exercise. Comparing dipyridamole and exercise, the differences in clearance were large from the early to the intermediate image (anterior, -11 +/- 17 versus 24 +/- 5, p = 0.0005; 50 degrees left anterior oblique, -7 +/- 11 versus 15 +/- 8, p = 0.004; 70 degrees left anterior oblique, 3 +/- 9 versus 21 +/- 6, p = 0.001). In contrast, the differences in clearance were small from the intermediate to the delayed image (anterior, 15 +/- 4 versus 20 +/- 2, p = 0.025; 50 degrees left anterior oblique, 15 +/- 4 versus 19 +/- 3, p = 0.13; 70 degrees left anterior oblique, 15 +/- 3 versus 18 +/- 2, p = 0.047). Thallium uptake and clearance in the liver, splanchnic region and spleen were greater after dipyridamole (p less than 0.001). Blood thallium levels were greater after dipyridamole (p less than 0.05) and cleared more slowly (p = 0.07). Thus, myocardial thallium-201 uptake and clearance after dipyridamole infusion differ from thallium kinetics after exercise. This difference is, in part, related to associated differences in extracardiac and blood kinetics. Diagnostic criteria for the detection of abnormal thallium-201 clearance must be specific for the type of intervention

  6. Phytochemical Screening and Evaluation of Cardioprotective Activity of Ethanolic Extract of Ocimum Basilicum L. (Basil Against Isoproterenol Induced Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Hamid Soraya

    2012-01-01

    Full Text Available Background and the purpose of the study: The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI.Methods: The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG's TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normalcontrol, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day for 2 consecutive days was used to induce MI.Results: Phytochemical screening indicated the presence of phenolic compounds (5.36% and flavonoids (1.86%.Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both inthe serum and the myocardium.Conclusion: The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities.

  7. Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil against isoproterenol induced myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Fathiazad Fatemeh

    2012-12-01

    Full Text Available Abstract Background and the purpose of the study The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI. Methods The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG's TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day for 2 consecutive days was used to induce MI. Results Phytochemical screening indicated the presence of phenolic compounds (5.36% and flavonoids (1.86%. Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium. Conclusion The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities.

  8. Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats

    Science.gov (United States)

    2012-01-01

    Background and the purpose of the study The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil) on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI). Methods The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG's TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used to induce MI. Results Phytochemical screening indicated the presence of phenolic compounds (5.36%) and flavonoids (1.86%). Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium. Conclusion The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities. PMID:23351503

  9. Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease

    International Nuclear Information System (INIS)

    Takeishi, Yasuchika; Chiba, Junya; Abe, Shinya

    1992-01-01

    Thallium-201 ( 201 Tl) myocardial perfusion imaging during adenosine infusion was performed in consecutive 55 patients with suspected coronary artery disease. Adenosine was infused intravenously at a rate of 0.14 mg/kg/min for 6 minutes and a dose of 111 MBq of 201 Tl was administered in a separate vein at the end of third minutes of infusion. Myocardial SPECT imaging was begun 5 minutes and 3 hours after the end of adenosine infusion. For evaluating the presence of perfusion defects, 2 short axis images at the basal and spical levels and a vertical long axis image at the mid left ventricle were used. The regions with decreased 201 Tl uptake were assessed semi-quantitatively. Adenosine infusion caused a slight reduction in systolic blood pressure and an increase in heart rate. The rate pressure products increased slightly (9314±2377 vs. 10360±2148, p 201 Tl myocardial imaging during adenosine infusion was considered to be safe and useful for evaluating the patients with ischemic heart disease. (author)

  10. Thrombolysis significantly reduces transient myocardial ischaemia following first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1992-01-01

    In order to investigate whether thrombolysis affects residual myocardial ischaemia, we prospectively performed a predischarge maximal exercise test and early out-of-hospital ambulatory ST segment monitoring in 123 consecutive men surviving a first acute myocardial infarction (AMI). Seventy...... less than 0.02). Thrombolysis resulted in a non-significant reduction in exercise-induced ST segment depression: prevalence 43% vs 62% in controls. However, during ambulatory monitoring the duration of transient myocardial ischaemia was significantly reduced in thrombolysed patients: 322 min vs 1144...... myocardial ischaemia. This may explain the improvement in myocardial function during physical activities, which was also observed in this study....

  11. Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis

    International Nuclear Information System (INIS)

    Humbert, T.; Luu-Duc, C.; Comet, M.; Demenge, P.

    1991-01-01

    Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl-β-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability that 201 Tl. Biodistribution studies of 1- 14 C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of 14 C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of 201 Tl and 14 C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of 14 C-IMPPA and necrotic foci size. Distributions of 14 C-IMPPA and 201 Tl in control rats' hearts were homogenous, like TTC staining. In infarcted hearts, areas of decreased 14 C-IMPPA uptake were nearly the same (100%±5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70%±5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging. (orig.)

  12. Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on attenuating the acute myocardium infarction-induced myocardial fibrosis in rat.

    Directory of Open Access Journals (Sweden)

    Jie-Ning Zhu

    Full Text Available Carvedilol, a nonselective β-adrenoreceptor antagonist, protects against myocardial injury induced by acute myocardium infarction (AMI. The mechanisms underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies have revealed the critical role of microRNAs (miRNAs in a variety of cardiovascular diseases. This study investigated whether miR-29b is involved in the cardioprotective effect of carvedilol against AMI-induced myocardial fibrosis. Male SD rats were randomized into several groups: the sham surgery control, left anterior descending (LAD surgery-AMI model, AMI plus low-dose carvedilol treatment (1 mg/kg per day, CAR-L, AMI plus medium-dose carvedilol treatment (5 mg/kg per day, CAR-M and AMI plus high-dose carvedilol treatment (10 mg/kg per day, CAR-H. Cardiac remodeling and impaired heart function were observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling, decreased ejection fraction, and fractional shortening were rescued in the CAR-M and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and α-SMA mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro study showed that Col1a1, Col3a1, and α-SMA were downregulated and miR-29b was upregulated by carvedilol in a dose-dependent manner in rat cardiac fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in downregulation of Col1a1, Col3a1, and α-SMA and upregulation of miR-29b derived from the miR-29b-2 precursor. Enforced expression of miR-29b significantly suppressed Col1a1, Col3a1, and α-SMA expression. Taken together, we found that smad3 inactivation and miR-29b upregulation contributed to the cardioprotective activity of carvedilol against AMI-induced myocardial fibrosis.

  13. Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on attenuating the acute myocardium infarction-induced myocardial fibrosis in rat.

    Science.gov (United States)

    Zhu, Jie-Ning; Chen, Ren; Fu, Yong-Heng; Lin, Qiu-Xiong; Huang, Shuai; Guo, Lin-Lin; Zhang, Meng-Zhen; Deng, Chun-Yu; Zou, Xiao; Zhong, Shi-Long; Yang, Min; Zhuang, Jian; Yu, Xi-Yong; Shan, Zhi-Xin

    2013-01-01

    Carvedilol, a nonselective β-adrenoreceptor antagonist, protects against myocardial injury induced by acute myocardium infarction (AMI). The mechanisms underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies have revealed the critical role of microRNAs (miRNAs) in a variety of cardiovascular diseases. This study investigated whether miR-29b is involved in the cardioprotective effect of carvedilol against AMI-induced myocardial fibrosis. Male SD rats were randomized into several groups: the sham surgery control, left anterior descending (LAD) surgery-AMI model, AMI plus low-dose carvedilol treatment (1 mg/kg per day, CAR-L), AMI plus medium-dose carvedilol treatment (5 mg/kg per day, CAR-M) and AMI plus high-dose carvedilol treatment (10 mg/kg per day, CAR-H). Cardiac remodeling and impaired heart function were observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling, decreased ejection fraction, and fractional shortening were rescued in the CAR-M and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and α-SMA mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro study showed that Col1a1, Col3a1, and α-SMA were downregulated and miR-29b was upregulated by carvedilol in a dose-dependent manner in rat cardiac fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in downregulation of Col1a1, Col3a1, and α-SMA and upregulation of miR-29b derived from the miR-29b-2 precursor. Enforced expression of miR-29b significantly suppressed Col1a1, Col3a1, and α-SMA expression. Taken together, we found that smad3 inactivation and miR-29b upregulation contributed to the cardioprotective activity of carvedilol against AMI-induced myocardial fibrosis.

  14. Effect of acupuncture on the genetic expression of myocardial endothelin-1 and atrial natriuretic peptide in rats with stress-induced prehypertension

    Directory of Open Access Journals (Sweden)

    Wenrui Jia

    2017-01-01

    Conclusion: Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats, suggesting a protective effect of acupuncture against myocardial damage.

  15. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  16. Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

    Directory of Open Access Journals (Sweden)

    Althaf Hussain Shaik

    2018-03-01

    Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

  17. Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report

    Directory of Open Access Journals (Sweden)

    Kontou-Fili Kalliopi

    2005-02-01

    Full Text Available Abstract Background Acute myocardial infarction (MI following anaphylaxis is rare, especially in subjects with normal coronary arteries. The exact pathogenetic mechanism of MI in anaphylaxis remains unclear. Case presentation The case of a 32-year-old asthmatic male with systemic anaphylaxis, due to oral intake of 500 mg amoxycillin, complicated by acute ST-elevation MI is the subject of this report. Following admission to the local Health Center and almost simultaneously with the second dose of subcutaneous epinephrine (0.2 mg, the patient developed acute myocardial injury. Coronary arteriography, performed before discharge, showed no evidence of obstructive coronary artery disease. In vivo allergological evaluation disclosed strong sensitivity to amoxycillin and the minor (allergenic determinants of penicillin. Conclusion Acute ST-elevation MI is a rare but potential complication of anaphylactic reactions, even in young adults with normal coronary arteries. Coronary artery spasm appears to be the main causative mechanism of MI in the setting of "cardiac anaphylaxis". However, on top of the vasoactive reaction, a thrombotic occlusion, induced by mast cell-derived mediators and facilitated by prolonged hypotension, cannot be excluded as a possible contributory factor.

  18. Comparison of myocardial blood flow induced by adenosine triphosphate and dipyridamole in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Mamede, M.; Tadamura, Eiji; Hosokawa, Ryohei

    2005-01-01

    Myocardial perfusion imaging with adenosine triphosphate (ATP) has been used increasingly to diagnose coronary artery disease (CAD) and assess risk for this disease. This study compared absolute myocardial blood flow (MBF) and myocardial flow reserve index (MFR) with ATP and dipyridamole (DIP) in patients with CAD. MBF was quantified by 15 O-H 2 O PET in 21 patients with CAD (17 male, 4 female), aged 55 to 81 years. MBF was measured at rest, during intravenous injection of ATP (0.16 mg/kg/min), and again after DIP infusion (0.56 mg/kg). Regions of interest were drawn in nonischemic and ischemic segments based on findings from thallium-201 ( 201 Tl) scintigraphy and coronary angiography (CAG). Absolute MBF values and indexes of MFR were calculated in nonischemic and ischemic segments. Intravenous injection of ATP and DIP significantly increased MBF in nonischemic (2.4±0.9 and 2.1±0.8 ml/g/min, respectively; p<0.01, for both) and in ischemic segments (1.3±0.4 and 1.5±0.4 ml/g/min, respectively; p<0.01, for both). There was a significant difference in MBF values between ATP and DIP in nonischemic segments (p<0.05), which was not observed in ischemic segments. In nonischemic segments, ATP produced higher MFR than DIP (2.1±0.8 and 1.8±0.7, respectively; p<0.05), while no significant difference was observed in ischemic segments (1.5±0.6 and 1.7±0.3, respectively). ATP produced a greater hyperemia than DIP between the ischemic and nonischemic myocardium in patients with CAD. ATP is as effective as DIP for the diagnosis of CAD. (author)

  19. Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

  20. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  1. Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Sachin Diwadkar

    2016-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity.

  2. Exogenous Nkx2.5- or GATA-4-transfected rabbit bone marrow mesenchymal stem cells and myocardial cell co-culture on the treatment of myocardial infarction in rabbits.

    Science.gov (United States)

    Li, Pu; Zhang, Lei

    2015-08-01

    The present study aimed to investigate the effects of Nkx2.5 or GATA-4 transfection with myocardial extracellular environment co-culture on the transformation of bone marrow mesenchymal stem cells (BMSCs) into differentiated cardiomyocytes. Nkx2.5 or GATA-4 were transfected into myocardial extracellular environment co-cultured BMSCs, and then injected into the periphery of infarcted myocardium of a myocardial infarction rabbit model. The effects of these gene transfections and culture on the infarcted myocardium were observed and the results may provide an experimental basis for the efficient myocardial cell differentiation of BMSCs. The present study also suggested that these cells may provide a source and clinical basis for myocardial injury repair via stem cell transplantation. The present study examined whether Nkx2.5 or GATA-4 exogenous gene transfection with myocardial cell extracellular environment co-culture were able to induce the differentiation of BMSCs into cardiac cells. In addition, the effect of these transfected BMSCs on the repair of the myocardium following myocardial infarction was determined using New Zealand rabbit models. The results demonstrated that myocardial cell differentiation was significantly less effective following exogenous gene transfection of Nkx2.5 or GATA-4 alone compared with that of transfection in combination with extracellular environment co-culture. In addition, the results of the present study showed that exogenous gene transfection of Nkx2.5 or GATA-4 into myocardial cell extracellular environment co-cultured BMSCs was able to significantly enhance the ability to repair, mitigating the death of myocardial cells and activation of the myocardium in rabbits with myocardial infarction compared with those of the rabbits transplanted with untreated BMSCs. In conclusion, the exogenous Nkx2.5 and GATA-4 gene transfection into myocardial extracellular environment co-cultured BMSCs induced increased differentiation into myocardial

  3. Experimentally induced helper dispersal in colonially breeding cooperative cichlids

    NARCIS (Netherlands)

    Heg, D.; Heg-Bachar, Z.; Brouwer, L.; Taborsky, M.

    2008-01-01

    The 'benefits of philopatry' hypothesis states that helpers in cooperatively breeding species derive higher benefits from remaining home, instead of dispersing and attempting to breed independently. We tested experimentally whether dispersal options influence dispersal propensity in the

  4. Effect of motion-induced PET-CT misalignment on cardiac function and myocardial blood flow measured using dynamic 15O-water PET

    DEFF Research Database (Denmark)

    Lubberink, Mark; Ebrahimi, M; Harms, Hans

    Aim: Motion-induced PET-CT misalignment artifacts are common in myocardial blood flow (MBF) measurements with 82Rb and 13N-ammonia. For 15O-water, MBF is based on the clearance rate rather than uptake of the tracer. The clearance rate is determined by the shape of the time-activity curve, not its......-CT misalignment on MBF, transmural MBF (MBFt), perfusable tissue fraction (PTF), cardiac output (CO), stroke volume (SV) and left-ventricular ejection fraction (LVEF) based on dynamic 15O-water scans. Methods: 10 patients underwent 6 min PET scans after injection of 400 MBq 15O-water at rest and during adenosine...

  5. Secoisolariciresinol diglucoside prevents the oxidative stress-induced apoptosis of myocardial cells through activation of the JAK2/STAT3 signaling pathway.

    Science.gov (United States)

    Huang, Guiqiong; Huang, Xiaofang; Liu, Min; Hua, Yue; Deng, Bo; Jin, Wen; Yan, Wen; Tan, Zhangbin; Wu, Yifen; Liu, Bin; Zhou, Yingchun

    2018-06-01

    Myocardial cell apoptosis mediated by oxidative stress has previously been identified as a key process in ischemic heart disease. Secoisolariciresinol diglucoside (SDG), a polyphenolic plant lignan primarily found in flaxseed, has been demonstrated to effectively protect myocardial cells from apoptosis. In the present study, the role of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was investigated in mediating the protective effect of SDG. Findings of the present study revealed that treatment with H2O2 reduced cell viability and induced apoptosis in H9C2 rat cardiomyocytes. However, SDG was able to reduce the effect of H2O2 in a dose‑dependent manner. H2O2 reduced the expression level of phosphorylated STAT3 and inhibited the levels of B‑cell lymphoma‑extra‑large and induced myeloid leukemia cell differentiation protein, which are the STAT3 target genes. Conversely, SDG rescued phosphorylation of STAT3 and increased the levels of STAT3 target genes. Treatment with SDG alone led to a dose‑dependent increased phosphorylation of JAK2 and STAT3, without activating Src. Furthermore, the anti‑apoptotic effects of SDG were partially abolished by a JAK2/STAT3 inhibitor. In addition, molecular docking revealed that SDG may bind to the protein kinase domain of JAK2, at a binding energy of ‑8.258 kcal/mol. Molecular dynamics simulations revealed that JAK2‑SDG binding was stable. In conclusion, activation of the JAK2/STAT3 signaling pathway contributed to the anti‑apoptotic activity of SDG, which may be a potential JAK2 activator.

  6. Imaging myocardial ischemia and reperfusion injury via Cy5.5 Annexin V

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Rong [Sichuan Univ., Chengdu (China); Pan, Dong Feng [Univ. of Virginia, VA (United States)

    2012-09-15

    The aim of this article is to present the results of an imaging study of myocardial apoptosis induced by ischemia/reperfusion injury. Twenty nude mice were randomly divided into an experimental group, myocardial apoptosis was induced by ligation of the left anterior descending coronary artery (LAD)for 30 min. This was followed by reperfusion for 90 min. In the control group, the heart was exposed for the same length of time as in the experimental group. Cy5.5 annexin V (25{mu}g)was injected into both sets of mice after the onset of reperfusion. At 90 min post injection, the mice were imaged. The region of interest (ROI)was obtained, and the fluorescence intensity of the ROI was quantified. The animals were sacrificed, and myocardial apoptosis was assayed by TUNEL assay. Fluorescence intensity in the ischemia/reperfusion hearts was significantly higher than that in the control group (P<0.05). In the TUNEL assay, more apoptotic cells were observed in the experimental group than in the control group, correlating with imaging results. Fluorescence imaging of Cy5.5 annexin V in a mouse model of myocardial ischemia/reperfusion can be used in vivo as a noninvasive means of detecting ischemia/reperfusion induced apoptotic cells in the heart.

  7. Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.

    Directory of Open Access Journals (Sweden)

    Chen Bian

    Full Text Available Luteolin (LUT, a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R. However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs. The purpose of this study was to determine which miRs and target genes LUT exerted such function through.Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets oncogene homolog 1. MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1.LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.

  8. Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.

    Science.gov (United States)

    Bian, Chen; Xu, Tongda; Zhu, Hong; Pan, Defeng; Liu, Yang; Luo, Yuanyuan; Wu, Pei; Li, Dongye

    2015-01-01

    Luteolin (LUT), a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R). However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs). The purpose of this study was to determine which miRs and target genes LUT exerted such function through. Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets) oncogene homolog 1). MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1. LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression. LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.

  9. An experimental study of 99Tcm-PnAO-nitroimidazole and 99Tcm-HL91 in detection of myocardial hypoxia

    International Nuclear Information System (INIS)

    Yao Zhiming; Liu Xiujie; Shi Rongfang; Guo Feng; Liu Yunzhong; Wang Qi; Wei Hongxing; Zhu Lin

    1999-01-01

    Objective: To investigate the biological characteristics of two hypoxic-avid imaging agents, 99 Tc m -PnAO-nitroimidazole and 99 Tc m -HL91, and the experimental myocardial hypoxia, low perfusion and ischemic reperfusion were performed. Methods: Isolated rat hearts were retrograde perfused with Kerbs-Henscleit buffer (KH) in four phantoms: control, low perfusion, ischemic reperfusion and hypoxia. Control hearts were perfused with 95% O 2 and 5% CO 2 balanced KH at 9∼10 mL/min rate. Low perfusion hearts were perfused with the same KH at 1 mL/min rate, and ischemic reperfusion rat hearts were discontinued perfusion for 20 min then reperfused with the same KH. Hypoxic hearts were perfused with 100% N 2 balanced KH. Results: 1) At 30 and 60 min, the radioactivity ratio of liver to heart (L/H) was 11.6 and 6.9 ( 99 Tc m -PnAO-nitroimidazole), and 5.7 and 6.2 ( 99 Tc m -HL91), respectively. The lung to heart ratios at 60 min of 99 Tc m -PnAO-nitroimidazole and 99 Tc m -HL91 were 1.8 and 2.1, respectively 2) The accumulation of 99 Tc m -PnAo-nitroimidazole in the hypoxic, low perfusion and ischemic hearts was 4.8, 3.7 and 2.8 times that in the control hearts. At 60 min after starting washout, the retentions of 99 Tc m -PnAO-nitroimidazole in hypoxic, low flow and ischemic reperfusion myocardium were much higher than that of control hearts [(23.7 +- 9.1)%]. The accumulation of 99 Tc m -HL91 in the hypoxic and low perfusion hearts was also significantly higher than that in the control and ischemic reperfusion hearts, P 99 Tc m -HL91 in the low perfusion heart was 5.34, 3.43 and 1.23 times those of control, ischemic reperfusion and hypoxic hearts, respectively. Conclusions: 99 Tc m -PnAO-nitroimidazole can be accumulated in low perfusion, ischemic reperfusion and hypoxic hearts, while 99 Tc m -HL91 is mainly accumulated in hypoxic, specially low perfusion hearts. Since there is a high L/H in perfusions with either agent, the detecting of inferoposterior wall may be

  10. Contagious equine metritis: clinical description of experimentally induced infection.

    Science.gov (United States)

    Pierson, R E; Sahu, S P; Dardiri, A H; Wilder, F W

    1978-08-15

    Contagious equine metritis was reproduced experimentally in 6 pony mares. The disease was characterized by rapidly developing cervicitis and by varying amounts of exudate. The exudate, apparent as early as 48 hours after inoculation, drained from the cervix as a tenacious, mucopurulent discharge for several days, then rapidly disappeared. In all mares, the clinical disease cleared within several weeks of inoculation, without treatment.

  11. Experimental observation of direct current voltage-induced phase ...

    Indian Academy of Sciences (India)

    The dynamics of two uncoupled distinct Chua circuits driven by a common direct current voltage is explored experimentally. It was found that, with increasing current intensity, the dominant frequencies of these two Chua circuits will first vary at different speeds, approach an identical value for a certain current intensity and ...

  12. Reversal of experimental varicocele-induced testicular toxicity by L ...

    African Journals Online (AJOL)

    testicular volumes, caudal epididymal sperm characteristics, testicular histology and serum hormone levels were evaluated. Results showed that the testes of the rats that were given vitamin C post experimental varicocele had better physiological, biochemical and histological profiles than those of the untreated animals.

  13. Influence of physical restraint on the onset of experimentally induced ...

    African Journals Online (AJOL)

    The role of intermittent repeated physical restraint on the onset of diabetes mellitus (DM) was in-vestigated in this study. The study compared the onset of DM in mice dosed with streptozotocin (STZ), a DM-inducing drug, with immediate subsequent exposure to either physical restraint stress or non- exposure to the stress.

  14. Pharmacokinetic changes of halofantrine in experimentally-induced ...

    African Journals Online (AJOL)

    It was hypothesized in this study that alterations in plasma lipoprotein profile and disturbed gastrointestinal motility as observed in diabetes mellitus may influence the disposition of halofantrine (HF), a highly lipophilic antimalarial drug. Therefore, using a rat model of diabetes mellitus induced by administration of alloxan ...

  15. Repair of experimental plaque-induced periodontal disease in dogs.

    Science.gov (United States)

    Shoukry, M; Ben Ali, L; Abdel Naby, M; Soliman, A

    2007-09-01

    Forty mongrel dogs were used in this study for induction of periodontal disease by placing subgingival silk ligatures affecting maxillary and mandibular premolar teeth during a 12-month period. Experimental premolar teeth received monthly clinical, radiographic, and histometric/pathologic assessments. The results demonstrated significant increases in scores and values of periodontal disease parameters associated with variable degrees of alveolar bone loss. The experimental maxillary premolar teeth exhibited more severe and rapid rates of periodontal disease compared with mandibular premolar teeth. Histometric analysis showed significant reduction in free and attached gingiva of the experimental teeth. Histopathological examination of buccolingual sections from experimental premolar teeth showed the presence of rete pegs within the sulcular epithelium with acanthosis and erosive changes, widening of the periodontal ligament, and alveolar bone resorption. Various methods for periodontal repair were studied in 194 experimental premolar teeth exhibiting different degrees of periodontal disease. The treatment plan comprised non-surgical (teeth scaling, root planing, and oral hygiene) and surgical methods (closed gingival curettage, modified Widman flap, and reconstructive surgery using autogenous bone marrow graft and canine amniotic membrane). The initial non-surgical treatment resulted in a periodontal recovery rate of 37.6% and was found effective for treatment of early periodontal disease based on resolution of gingivitis and reduction of periodontal probing depths. Surgical treatment by closed gingival curettage to eliminate the diseased pocket lining resulted in a recovery rate of 48.8% and proved effective in substantially reducing deep periodontal pockets. Open root planing following flap elevation resulted in a recovery rate of 85.4% and was effective for deep and refractory periodontal pockets. Autogenous bone graft implantation combined with canine amniotic

  16. Activation of Na+-K+-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na+-K+-ATPase/Src/Ros amplifier.

    Science.gov (United States)

    Yan, Xiaofei; Xun, Meng; Dou, Xiaojuan; Wu, Litao; Zhang, Fujun; Zheng, Jin

    2017-04-01

    Reduced Na + -K + -ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na + -K + -ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na + /K + -ATPase's DR-region specific monoclonal antibody and direct activator, could disrupt Na + -K + -ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H 2 O 2 )-induced cardiac cell injury and mitochondrial dysfunction. DRm217 also alleviated the effect of H 2 O 2 on inhibition of Na + -K + -ATPase activity, Na + -K + -ATPase cell surface expression, and Src phosphorylation. H 2 O 2 -treatment increased intracellular ROS, mitochondrial ROS and induced intracellular Ca 2+ , mitochondrial Ca 2+ overload. DRm217 closed Na + -K + -ATPase/ROS amplifier, alleviated Ca 2+ accumulation and finally inhibited ROS and mitochondrial ROS generation. These novel results may help us to understand the important role of the Na + -K + -ATPase in oxidative stress and oxidative stress-related disease.

  17. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction

    DEFF Research Database (Denmark)

    González-Santamaría, José; Villalba, María; Busnadiego, Oscar

    2016-01-01

    resulted in reduced ventricular dilatation and improved cardiac function. CONCLUSION: LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery....... contributed to the induction of LOX expression in cardiac fibroblasts. Finally, in vivo post-infarction treatment with the broadband LOX inhibitor β-aminopropionitrile or, selectively, with a neutralizing antibody against the canonical LOX isoform attenuated collagen accumulation and maturation and also......AIMS: After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular...

  18. Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure

    Directory of Open Access Journals (Sweden)

    Julia Pohl

    2017-10-01

    Full Text Available Macrophage migration inhibitory factor (MIF is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF-1α. We here report on MIF expression in the failing human heart and assess myocardial MIF in different types of cardiomyopathy. Myocardial tissue samples from n = 30 patients were analyzed by quantitative Real-Time PCR. MIF and HIF-1α mRNA expression was analyzed in myocardial samples from patients with ischemic (ICM and non-ischemic cardiomyopathy (NICM and from patients after heart transplantation (HTX. MIF expression was elevated in myocardial samples from patients with ICM compared to NICM. Transplanted hearts showed lower MIF levels compared to hearts from patients with ICM. Expression of HIF-1α was analyzed and was shown to be significantly increased in ICM patients compared to patients with NICM. MIF and HIF-1α mRNA is expressed in the human heart. MIF and HIF-1α expression depends on the underlying type of cardiomyopathy. Patients with ICM show increased myocardial MIF and HIF-1α expression.

  19. Experimental analysis of recombination and neutralization of radiation-induced charges, using isochronal annealing

    International Nuclear Information System (INIS)

    Quittard, O.; Brisset, C.; Joffre, F.; Oudea, C.; Saigne, F.; Dusseau, L.; Fesquet, J.; Gasiot, J.

    1999-01-01

    The experimental analysis described in this paper made use of the isochronal principle to carry out qualitative and quantitative studies of both aspects of the RICN mechanism (radiation-induced charge neutralization) : recombination and compensation. (authors)

  20. Host response in bovine mastitis experimentally induced with Staphylococcus chromogenes.

    Science.gov (United States)

    Simojoki, H; Orro, T; Taponen, S; Pyörälä, S

    2009-02-16

    An experimental infection model was developed to study host response to intramammary infection in cows caused by Staphylococcus chromogenes. CNS intramammary infections have become very common in modern dairy herds, and they can remain persistent in the mammary gland. More information would be needed about the pathophysiology of CNS mastitis, and an experimental mastitis model is a means for this research. Six primiparous Holstein-Friesian cows were challenged with S. chromogenes 4 weeks after calving. One udder quarter of each cow was inoculated with 2.1 x 10(6)cfu of S. chromogenes. All cows became infected and clinical signs were mild. Milk production of the challenged quarter decreased on average by 16.3% during 7 days post-challenge. Cows eliminated bacteria in a few days, except for one cow which developed persistent mastitis. Milk indicators of inflammation, SCC and N-acetyl-beta-D-glucosaminidase (NAGase) returned to normal within a week. Milk NAGase activity increased moderately, which reflects minor tissue damage in the udder. Concentrations of serum amyloid A (SAA) and milk amyloid A (MAA) were both elevated at 12h PC. MAA was affected by the milking times, and was at its highest before the morning milking. In our experimental model, systemic acute phase protein response with SAA occurred as an on-off type reaction. In conclusion, this experimental model could be used to study host response in CNS mastitis caused by the main CNS species and also for comparison of the host response in a mild intramammary infection and in more severe mastitis models.

  1. Effect of beta-blockade on low-dose dobutamine-induced changes in left ventricular function in healthy volunteers: assessment by gated SPET myocardial perfusion scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Everaert, H.; Vanhove, C.; Franken, P.R. [Division of Nuclear Medicine, University Hospital, Free University of Brussels (AZ VUB), Brussels (Belgium)

    2000-04-01

    Viability studies are often performed in patients receiving beta-blocking agents. However, the intake of beta-blocking agents could influence the identification of viable myocardium when low-dose dobutamine is used to demonstrate inotropic reserve. The aim of this study was to quantify the effect of beta-blockade on global and regional left ventricular function in healthy volunteers using low-dose dobutamine gated single-photon emission tomographic (SPET) myocardial perfusion scintigraphy. Ten subjects were studied once ''on'' and once ''off'' beta-blocker therapy (metoprolol succinate, 100 mg day{sup -1}). On each occasion four consecutive gated SPET acquisitions (of 7 min duration) were recorded after injection of 925 MBq technetium-99m tetrofosmin on a triple-headed camera equipped with focussing (Cardiofocal) collimators. Acquisitions were made at rest (baseline 1 and 2) and 5 min after the beginning of the infusion of 5 and 10 {mu}g kg{sup -1} min{sup -1} dobutamine. Wall thickening (WT) was quantified using a method based on circumferential profile analysis. Left ventricular ejection fraction (LVEF) was obtained using the Cedars-Sinai algorithm. Blood pressure (BP) and heart rate (HR) were recorded at the end of each acquisition. At baseline LVEF, WT and systolic BP values under beta-blockade were not significantly different from those obtained in the non-beta-blocked state. The mean HR and diastolic BP at baseline were lower under beta-blockade. Dobutamine administration (at 5 and 10 {mu}g kg{sup -1} min{sup -1}) induced a significant increase in WT, LVEF and systolic BP in all subjects both on and off beta-blockade. The increases in WT, LVEF and systolic BP in the beta-blocked state were less pronounced but not significantly different. HR increased significantly at 10 {mu}g kg{sup -1} min{sup -1} dobutamine without beta-blocker administration, while no increase in HR was observed in the beta-blocked state. Beta

  2. Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

    Science.gov (United States)

    Wang, Zheng; Guo, Qiong-Ya; Zhang, Xiao-Ju; Li, Xiao; Li, Wen-Ting; Ma, Xi-Tao; Ma, Li-Jun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1β, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-β1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-β1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis. PMID:24886817

  3. The effect of levosimendan on myocardial ischemiareperfusion ...

    African Journals Online (AJOL)

    The effect of levosimendan on myocardial ischemiareperfusion injury in streptozotocin-induced diabetic rats. Hasan Ali Kiraz, Fatih Poyraz, Gulay Kip, Ozlem Erdem, Metin Alkan, Mustafa Arslan, Abdullah Ozer, Volkan Sivgin, Faruk Metin Comu ...

  4. Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction

    Directory of Open Access Journals (Sweden)

    Melissa Touvron

    2012-07-01

    Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs, which leads to cardiac dysfunction and heart failure (HF. Connective tissue growth factor (CTGF, a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized. We investigated the consequences of expressing a cardiac-specific transgene encoding locally acting IGF1 propeptide (muscle-produced IGF1; mIGF1 on disease progression in a mouse model of DCM [cardiac-specific and inducible serum response factor (SRF gene disruption] that mimics some forms of human DCM. Cardiac-specific mIGF1 expression substantially extended the lifespan of SRF mutant mice, markedly improved cardiac functions, and delayed both DCM and HF. These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. At least some of the beneficial effects of mIGF1 transgene expression were due to mIGF1 counteracting the strong increase in CTGF expression within cardiomyocytes caused by SRF deficiency, resulting in the blockade of fibroblast proliferation and related myocardial fibrosis. These findings demonstrate that SRF plays a key role in the modulation of cardiac fibrosis through repression of cardiomyocyte CTGF expression in a paracrine fashion. They also explain how impaired SRF function observed in human HF promotes fibrosis and adverse cardiac remodeling. Locally acting mIGF1 efficiently protects the myocardium from these adverse processes, and might thus represent a therapeutic avenue to counter DCM.

  5. β(3)-Adrenoceptor Antagonist SR59230A Attenuates the Imbalance of Systemic and Myocardial Oxygen Transport Induced by Dopamine in Newborn Lambs.

    Science.gov (United States)

    Gill, Richdeep S; Cheung, Po-Yin; Yu, Xiaoyang; Aklabi, Mohammed Al; Nagendran, Jeevan; Quinonez, Luis G; Li, Ying Qian; Miller, John; Ross, David B; Rebeyka, Ivan M; Li, Jia

    2012-01-01

    In neonates, the increase in O(2)-delivery (DO(2)) by dopamine is offset by a greater increase in O(2)-consumption (VO(2)). This has been attributed to β(3)-adrenergic receptors in neonatal brown fat tissue. β(3) receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a β(3)-antagonist, on the balance of systemic and myocardial O(2)-transport in newborn lambs treated with dopamine. Lambs (2-5 days old, n = 12) were anesthetized and mechanically ventilated. Heart rate (HR) and rectal temperature were monitored. VO(2) was measured by respiratory mass spectrometry and cardiac output (CO) by a pulmonary artery transonic flowmeter. Arterial, jugular bulb venous and coronary sinus blood gases and lactate were measured to calculate DO(2), O(2) extraction ratio (ERO(2)), myocardial O(2) and lactate extraction ratios (mERO(2), mERlac). After baseline measurements, lambs were randomized to receive SR59230A at 5 mg/kg iv (SRG) or placebo. Both groups received incremental doses of a dopamine infusion (0-5-10-15-20 mcg/kg/min) every 15 min. Measurements were repeated at the end of each dose. After SR59230A infusion, CO and HR trended to decrease (P = 0.06), but no significant changes occurred in other parameters. Over the incremental doses of dopamine, temperature increased in both groups (P 0.1). DO(2) trended to a small increase (P = 0.08). VO(2) increased in both groups (P transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR59230A in cases of cardiac dysfunction and increased VO(2), observed after cardiac surgery.

  6. Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model.

    Science.gov (United States)

    Khanna, Ashwani K; Xu, Jianping; Mehra, Mandeep R

    2012-02-01

    The contribution of chronic tobacco exposure in determining post-myocardial infarction (MI) left ventricular (LV) remodeling and possible therapeutic strategies has not been investigated systematically. In this small animal investigation, we demonstrate that chronic tobacco smoke exposure leading up to acute MI in rats is associated with greater histological extent of myocardial necrosis and consequent worse LV function. These findings are associated with increased transcriptomic expression of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress in the myocardium. The results demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced tobacco-exposed induced infarct size and percent fractional shortening. A significantly increased LV end-systolic diameter was observed in tobacco-exposed sham compared to tobacco-naïve sham (4.92±0.41 vs 3.45±0.33; Ptobacco-exposed MI compared to tobacco-naïve MI (8.24±0.3 vs 6.1±0.49; Ptobacco-exposed MI rats with NAC resulted in significantly increased levels of intracardiac mRNA expression of antioxidants, including superoxide dismutase, thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels of glutathione (7±0.12 vs 10±0.18; P≤0.001), where the levels were almost identical to the tobacco-naïve sham rats. These findings identify a novel post-infarction therapy for amelioration of the adverse effects of tobacco exposure on the infracted myocardium and advocate the use of dietary supplement antioxidants for habitual smokers to prevent and reverse cardiovascular adverse effects in the absence of successful achievement of cessation of smoking.

  7. Ovine keratoconjunctivitis experimentally induced by instillation of Mycoplasma conjunctivae.

    Science.gov (United States)

    ter Laak, E A; Schreuder, B E; Kimman, T G; Houwers, D J

    1988-10-01

    Five sheep, free from Mycoplasma conjunctivae and ocular Chlamydia infection, were experimentally inoculated with M. conjunctivae and five more sheep were exposed to the infection by contact. Keratoconjunctivitis developed in all ten sheep. As in natural outbreaks of infectious keratoconjunctivitis (IKC), clinical signs were generally moderate and transient, and recurred in some sheep. M. conjunctivae was detected throughout the 53-day observation period. Clinical diagnosis was confirmed by histopathologic examination of three sheep. Moraxella ovis, found in six of the ten sheep before the start of the experiment, appeared to play no etiologic role in the development of IKC.

  8. Appraisal of experimental and commercial Marek's disease vaccines to induce bursal and thymic atrophy

    Science.gov (United States)

    Recently, several experimental Marek’s disease (MD) vaccines were developed that appear to protect equally or better than the best commercial vaccines. However, some of the experimental vaccines were reported to induce transient bursal and thymic atrophies. We will report on two promising experiment...

  9. Experimental research on recombinant human endostatin-induced cardiomyocyte apoptosis in rats

    Directory of Open Access Journals (Sweden)

    Jing QIN

    2014-03-01

    Full Text Available Objective To explore the recombinant human endostatin (rh-ES-induced cardiotoxicity in rats and its mechanism. Methods Twenty four female Wistar rats were randomly divided into four groups (6 each. Rats in low, moderate and high dose group received rh-ES with a dosage of 3, 6 and 12mg/(kg·d, respectively, by intraperitoneal injection, and rats in control group received the same amount of normal saline alone. Half of rats in each group were sacrificed by spinal dislocation after 4 weeks and 8 weeks of the treatment. Pathomorphologic and ultrastructural changes in rat's myocardial tissue were evaluated by light microscopy and transmission electron microscopy. Cardiomyocyte apoptosis was detected with TdT-mediated dUTP nick end labeling (TUNEL assay. Microvessel density (MVD in myocardial tissue was measured by immunohistochemically marking endothelial cell with CD34. Results No pathomorphologic and ultrastrucural changes were found under light microscope and transmission electron microscope in the low dose and moderate dose groups, but cardiomyocyte damage were found in the high dose group. TUNEL assay revealed more apoptotic cells in high and moderate (only 8 weeks dose groups than in control group (P=0.033, P=0.000, and the apoptosis index was highest in the high dose group at 8 weeks. In addition, compared with the control group, MVD significantly increased in high dose groups at 4 weeks and 8 weeks (P<0.05. Conclusions rh-ES induces the cardiotoxicity in rats, and cardiomyocyte apoptosis is involved in the pathological course of cardiac toxicity. DOI: 10.11855/j.issn.0577-7402.2014.01.02

  10. Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy

    International Nuclear Information System (INIS)

    Prior, John O.; Calcagni, Maria-Lucia; Bischof Delaloye, Angelika; Monbaron, David; Ruiz, Juan; Koehli, Melanie

    2005-01-01

    Silent myocardial ischaemia - as evaluated by stress-induced perfusion defects on myocardial perfusion scintigraphy (MPS) in patients without a history of chest pain - is frequent in diabetes and is associated with increased rates of cardiovascular events. Its prevalence has been determined in asymptomatic diabetic patients, but remains largely unknown in diabetic patients with suspected coronary artery disease (CAD) in the clinical setting. In this study we therefore sought (a) to determine the prevalence of symptomatic and silent perfusion defects in diabetic patients with suspected CAD and (b) to characterise the eventual predictors of abnormal perfusion. The patient population comprised 133 consecutive diabetic patients with suspected CAD who had been referred for MPS. Studies were performed with exercise (41%) or pharmacological stress testing (1-day protocol, 99m Tc-sestamibi, 201 Tl or both). We used semi-quantitative analysis (20-segment polar maps) to derive the summed stress score (SSS) and the summed difference score (SDS). Abnormal MPS (SSS≥4) was observed in 49 (37%) patients (SSS=4.9±8.4, SDS=2.4±4.7), reversible perfusion defects (SDS≥2) in 40 (30%) patients [SSS=13.3±10.9; SDS=8.0±5.6; 20% moderate to severe (SDS>4), 7% multivessel] and fixed defects in 21 (16%) patients. Results were comparable between patients with and patients without a history of chest pain. Of 75 patients without a history of chest pain, 23 (31%, 95% CI=21-42%) presented reversible defects (SSS=13.9±11.3; SDS=7.4±1.2), indicative of silent ischaemia. Reversible defects were associated with inducible ST segment depression during MPS stress (odds ratio (OR)=3.2, p<0.01). Fixed defects were associated with erectile dysfunction in males (OR=3.7, p=0.02) and lower aspirin use (OR=0.25, p=0.02). Silent stress-induced perfusion defects occurred in 31% of the patients, a rate similar to that in patients with a history of chest pain. MPS could identify these patients with a

  11. Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Prior, John O.; Calcagni, Maria-Lucia; Bischof Delaloye, Angelika [Centre Hospitalier Universitaire Vaudois (CHUV University Hospital), Division of Nuclear Medicine, Lausanne (Switzerland); Monbaron, David; Ruiz, Juan [Centre Hospitalier Universitaire Vaudois (CHUV University Hospital), Division of Endocrinology, Diabetology and Metabolism, Lausanne (Switzerland); Koehli, Melanie [Centre Hospitalier Universitaire Vaudois (CHUV University Hospital), Division of Nuclear Medicine, Lausanne (Switzerland); Centre Hospitalier Universitaire Vaudois (CHUV University Hospital), Division of Endocrinology, Diabetology and Metabolism, Lausanne (Switzerland)

    2005-01-01

    Silent myocardial ischaemia - as evaluated by stress-induced perfusion defects on myocardial perfusion scintigraphy (MPS) in patients without a history of chest pain - is frequent in diabetes and is associated with increased rates of cardiovascular events. Its prevalence has been determined in asymptomatic diabetic patients, but remains largely unknown in diabetic patients with suspected coronary artery disease (CAD) in the clinical setting. In this study we therefore sought (a) to determine the prevalence of symptomatic and silent perfusion defects in diabetic patients with suspected CAD and (b) to characterise the eventual predictors of abnormal perfusion. The patient population comprised 133 consecutive diabetic patients with suspected CAD who had been referred for MPS. Studies were performed with exercise (41%) or pharmacological stress testing (1-day protocol, {sup 99m}Tc-sestamibi, {sup 201}Tl or both). We used semi-quantitative analysis (20-segment polar maps) to derive the summed stress score (SSS) and the summed difference score (SDS). Abnormal MPS (SSS{>=}4) was observed in 49 (37%) patients (SSS=4.9{+-}8.4, SDS=2.4{+-}4.7), reversible perfusion defects (SDS{>=}2) in 40 (30%) patients [SSS=13.3{+-}10.9; SDS=8.0{+-}5.6; 20% moderate to severe (SDS>4), 7% multivessel] and fixed defects in 21 (16%) patients. Results were comparable between patients with and patients without a history of chest pain. Of 75 patients without a history of chest pain, 23 (31%, 95% CI=21-42%) presented reversible defects (SSS=13.9{+-}11.3; SDS=7.4{+-}1.2), indicative of silent ischaemia. Reversible defects were associated with inducible ST segment depression during MPS stress (odds ratio (OR)=3.2, p<0.01). Fixed defects were associated with erectile dysfunction in males (OR=3.7, p=0.02) and lower aspirin use (OR=0.25, p=0.02). Silent stress-induced perfusion defects occurred in 31% of the patients, a rate similar to that in patients with a history of chest pain. MPS could identify

  12. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia.

    Directory of Open Access Journals (Sweden)

    Kenichiro Hanawa

    Full Text Available Although a significant progress has been made in the management of ischemic heart disease (IHD, the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS therapy for the treatment of IHD.We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF with a peak at 32-cycle (P<0.05. Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF (n = 28. The heart was treated with either sham (n = 14 or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14 at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05 without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33. Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05. Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05, but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g. Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group.These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

  13. Neuroprotective effect of melatonin in experimentally induced hypobaric hypoxia.

    Science.gov (United States)

    Vornicescu, Corina; Boşca, Bianca; Crişan, Doiniţa; Yacoob, Sumaya; Stan, Nora; Filip, Adriana; Şovrea, Alina

    2013-01-01

    Melatonin (MEL) is an endogenous neurohormone with many biological functions, including a powerful antioxidant effect. The aim of the present study was to determine whether MEL protects the brain tissue from the oxidative stress induced by hypobaric hypoxia (HH) in vivo. This study was performed on Wistar rats randomly assigned in four groups, according to the pressure conditions and treatment: Group 1: normoxia and placebo; Group 2: HH and placebo; Group 3: normoxia and MEL; and Group 4: HH and MEL. The following aspects were evaluated: cognitive function (space reference and memory), oxidative stress parameters - serum and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels -, and brain tissue macroscopic and microscopic morphological changes. Exposure to oxidative stress results in cognitive dysfunctions and biochemical alterations: significant increase of MDA and reduction of GSH in both serum and brain tissue. The most important morphological changes were observed in Group 2: increased cellularity, loss of pericellular haloes, shrunken neurons with scanty cytoplasm and hyperchromatic, pyknotic or absent nuclei; reactive gliosis, edema and blood-brain barrier alterations could also be observed in some areas. MEL treatment significantly diminished all these effects. Our results suggest that melatonin is a neuroprotective antioxidant both in normoxia and hypobaric hypoxia that can prevent and counteract the deleterious effects of oxidative stress (neuronal death, reactive astrogliosis, memory impairment and cognitive dysfunctions). Dietary supplements containing melatonin might be useful neuroprotective agents for the therapy of hypoxia-induced consequences.

  14. An experimental investigation of proton-induced phenomena in krypton

    International Nuclear Information System (INIS)

    Mulders, J.J.L.

    1985-01-01

    In this thesis proton-induced phenomena in krypton gas are described. The considered reactions of protons on krypton are both nuclear and atomic. The nuclear conversion processes mainly result in the production of several Rb radioisotopes, such as 81 Rb that is used in 81 Rb-sup(81m)Kr generator systems for medical diagnostics. The irradiation of krypton gas (natural composition) with protons of about 26 MeV can be used for the routine production of 81 Rb from the direct production reaction 82 Kr(p,2n) 81 Rb and from the indirect reaction 82 Kr(p,2n)sup(81m)Rb → 81 Rb. To determine the scattering of protons in krypton gas targets a quantitative autoradiographic technique was developed. Proton profiles have been determined from the proton-induced activity distribution on a copper foil. For the on-line detection of produced Rb radioisotopes several optical detection techniques were investigated. (Auth.)

  15. [Fetal experimentation, transplantations, cosmetics and their connection with induced abortion].

    Science.gov (United States)

    Redondo Calderón, José Luis

    2012-01-01

    The increase in induced abortion produces large numbers of cells, tissues and organs, which are used in several fields of Medicine, either in research or in treatment. The main uses are in Cardiology, Hematology, Metabolism, Embryology, Neurology, Immunology, Ophthalmology, Dermatology and Transplantations. Flavor enhancers and cosmetics also benefit. Utilitarianism has led to an increase in abortion-originated cell and tissue banks. Abortion is justified through the manipulation of language. Vested interests give rise to complicity in researchers and society as a whole. Abortion and tissue 'donation' cannot be split; since fresh tissues are involved there is a symbiotic relationship between them. Valid consent is not possible. A contradiction emerges, the nasciturus is not desired or valued but fetal organs are. When someone is deprived of his rights it is because another wants to enslave them. Research must have a moral base. Knowledge should not be increased at any price. Something that is legal and well intentioned is not always morally acceptable. The duty of omission is applicable. Means to achieve a goal must be ethical means. Educational efforts to restore respect for the human embryo and fetus must be promoted. Technical advances are not always in accordance with human nature and dignity. Research and treatment that do not resort to cells, tissues and organs obtained from induced abortions should be promoted.

  16. Experimental gentamicin-induced nephrotoxicity in the sheep

    Directory of Open Access Journals (Sweden)

    Fartashvand Majid

    2014-12-01

    Full Text Available The aim of the study was to investigate the nephrotoxic effects of gentamicin in adult male sheep, and to identify the earliest signs of toxicity and the extent of clinical and biochemical changes. Twenty clinically healthy yearling male Iranian fattailed sheep were injected with gentamicin sulfate at a daily dose of 80 mg/kg for 9-10 d when nephrotoxicosis was induced. Blood samples were collected weekly before and after induction of nephrotoxicosis. Gentamicin-induced nephrotoxicity was characterised by increased creatinine and urea levels in serum, electrolyte imbalances, occurrence of albuminuria, and renal dysfunction. Significant elevation in respiratory and heart rates were observed one week after treatment (P < 0.05. There was a noticeable increase in water consumption, lethargy, and loss of appetite in treated sheep. There were significant correlations between serum creatinine and potassium (P = 0.004, r = 0.759, sodium (P = 0.017, r = 0.501, and urea (P = 0.021, r = 0.617 levels. Additionally, significant negative correlations between serum total protein and albumin and creatinine (P = 0.023, r = -0.484 and urea (P = 0.036, r = -0.381 were found. At necropsy, the kidneys were pale, swollen, and wet on the cut surface, especially perirenal tissues and ureters were oedematous. These findings confirmed the previous reports in other species.

  17. Mesenchymal Stem Cells Induce Expression of CD73 in Human Monocytes In Vitro and in a Swine Model of Myocardial Infarction In Vivo

    Directory of Open Access Journals (Sweden)

    Marta Monguió-Tortajada

    2017-11-01

    Full Text Available The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP/ADP to AMP and to adenosine (Ado, respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity. In addition, the local treatment with porcine cATMSCs using an engineered bioactive graft promoted the in vivo CD73 expression on host monocytes in a swine model of myocardial infarction. Our results suggest the upregulation of ectonucleotidases on MSC-conditioned monocytes as an effective mechanism to amplify the long-lasting immunomodulatory and healing effects of MSCs delivery.

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

    Directory of Open Access Journals (Sweden)

    Jiaojiao Pang

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

  19. Experimentation and numerical modeling of forging induced bending (FIB) process

    Science.gov (United States)

    Naseem, S.; van den Boogaard, A. H.

    2016-10-01

    Accurate prediction of the final shape using numerical modeling has been a top priority in the field of sheet and bulk forming. Better shape prediction is the result of a better estimation of the physical stress and strain state. For experimental and numerical investigations of such estimations, simple benchmark processes are used. In this paper a benchmark process involving forging (flattening) of sheet metal between punch and die with negative clearance is proposed. The introduced material flow results in bending. Easy measurability of the angle of this bend makes this process suitable for validation purpose. Physical experiments are performed to characterize this bending angle due to flattening. Furthermore a numerical model is developed to capture this phenomenon. The main focus of this paper is the validation of the numerical model in terms of accurate prediction of the physical results.

  20. Alleviating effects of morin against experimentally-induced diabetic osteopenia

    Directory of Open Access Journals (Sweden)

    Abuohashish Hatem M

    2013-02-01

    Full Text Available Abstract Background Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of aging diseases particularly bone metabolic disorders. Morin (3,5,7,20,40-pentahydroxyflavone, a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. The present study was designed to investigate the putative beneficial effect of morin on diabetic osteopenia in rats. Methods Streptozotocin (STZ-induced diabetic model was used by considering 300 mg/dl fasting glucose level as diabetic. Morin (15 and 30 mg/kg was treated for five consecutive weeks to diabetic rats. Serum levels of glucose, insulin, deoxypyridinoline cross links (DPD, osteocalcin (OC, bone specific alkaline phosphatase (BALP, telopeptides of collagen type I (CTX, interleukin 1 beta (IL-1β, interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, thiobarbituric acid reactive substance (TBARS and reduced glutathione (GSH were estimated. Femoral bones were taken for micro CT scan to measure trabecular bone mineral density (BMD and other morphometric parameters. Results Significant bone loss was documented as the level of bone turnover parameters including DPD, OC, BALP and CTX were increased in serum of diabetic rats. Morin treatment significantly attenuated these elevated levels. Bone micro-CT scan of diabetic rats showed a significant impairment in trabecular bone microarchitecture, density and other morphometric parameters. These impairments were significantly ameliorated by morin administration. Serum levels of glucose, TBARS, IL-1β, IL-6 and TNF-α were significantly elevated, while the level of insulin and GSH was decreased in diabetic rats. These serum changes in diabetic rats were bring back to normal values after 5 weeks morin treatment. Conclusion These findings revealed the protective effect of morin against diabetic induced osteopenia. We believed that this effect is through its both the anti

  1. A Comparison of Theory-Based and Experimentally Determined Myocardial Signal Intensity Correction Methods in First-Pass Perfusion Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Jacob U. Fluckiger

    2015-01-01

    Full Text Available Objectives. To evaluate the impact of correcting myocardial signal saturation on the accuracy of absolute myocardial blood flow (MBF measurements. Materials and Methods. We performed 15 dual bolus first-pass perfusion studies in 7 dogs during global coronary vasodilation and variable degrees of coronary artery stenosis. We compared microsphere MBF to MBF calculated from uncorrected and corrected MRI signal. Four correction methods were tested, two theoretical methods (Th1 and Th2 and two empirical methods (Em1 and Em2. Results. The correlations with microsphere MBF (n=90 segments were: uncorrected (y=0.47x+1.1, r=0.70, Th1 (y=0.53x+1.0, r=0.71, Th2 (y=0.62x+0.86, r=0.73, Em1 (y=0.82x+0.86, r=0.77, and Em2 (y=0.72x+0.84, r=0.75. All corrected methods were not significantly different from microspheres, while uncorrected MBF values were significantly lower. For the top 50% of microsphere MBF values, flows were significantly underestimated by uncorrected SI (31%, Th1 (25%, and Th2 (19%, while Em1 (1%, and Em2 (9% were similar to microsphere MBF. Conclusions. Myocardial signal saturation should be corrected prior to flow modeling to avoid underestimation of MBF by MR perfusion imaging.

  2. Myocardial perfusion modeling using MRI

    DEFF Research Database (Denmark)

    Larsson, H B; Fritz-Hansen, T; Rostrup, Egill

    1996-01-01

    In the present study, it is shown that it is possible to quantify myocardial perfusion using magnetic resonance imaging in combination with gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA). Previously, a simple model and method for measuring myocardial perfusion using an inversion recovery...... of Gd-DTPA (lambda), the vascular blood volume (Vb), and the time delay through the coronary arteries (delta T). The model was evaluated by computer simulation and used on experimental results from seven healthy subjects. The results in the healthy volunteers for a region of interest placed...... in the anterior myocardial wall were (mean +/- SD) Ki = 54 +/- 10 ml/100 g/min, lambda = 30 +/- 3 ml/100 g, Vb = 9 +/- 2 ml/100 g, delta T = 3.2 +/- 1.1 s. These results are in good agreement with similar results obtained by other methods....

  3. Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.

    Science.gov (United States)

    Mohiti-Asli, M; Ghanaatparast-Rashti, M

    2015-06-15

    An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    Science.gov (United States)

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-09-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

  5. A soluble receptor for advanced glycation end-products inhibits myocardial apoptosis induced by ischemia/reperfusion via the JAK2/STAT3 pathway.

    Science.gov (United States)

    Jiang, Xue; Guo, Cai-xia; Zeng, Xiang-jun; Li, Hui-hua; Chen, Bu-xing; Du, Feng-he

    2015-08-01

    sRAGE can protect cardiomyocytes from apoptosis induced by ischemia/reperfusion (I/R). However, the signaling mechanisms in cardioprotection by sRAGE are currently unknown. We investigated the cardioprotective effect and potential molecular mechanisms of sRAGE inhibition on apoptosis in the mouse myocardial I/R as an in vivo model and neonatal rat cardiomyocyte subjected to ischemic buffer as an in vitro model. Cardiac function and myocardial infarct size following by I/R were evaluated with echocardiography and Evans blue/2,3,5-triphenyltetrazolium chloride. Apoptosis was detected by TUNEL staining and caspase-3 activity. Expression of the apoptosis-related proteins p53, Bax, Bcl-2, JAK2/p-JAK2, STAT3/p-STAT3, AKT/p-AKT, ERK/p-ERK, STAT5A/p-STAT5A and STAT6/p-STAT6 were detected by western blot analysis in the presence and absence of the JAK2 inhibitor AG 490. sRAGE (100 µg/day) improved the heart function in mice with I/R: the left ventricular ejection fraction and fractional shortening were increased by 42 and 57%, respectively; the infarct size was decreased by 52%, the TUNEL-positive myocytes by 66%, and activity of caspase-3 by 24%, the protein expression of p53 and ratio of Bax to Bcl-2 by 29 and 88%, respectively; protein expression of the p-JAK2, p-STAT3 and p-AKT were increased by 92, 280 and 31%, respectively. sRAGE have no effect on protein expression of p-ERK1/2, p-STAT5A and p-STAT6 following by I/R. sRAGE (900 nmol/L) exhibited anti-apoptotic effects in cardiomyocytes by decreasing TUNEL-positive myocytes by 67% and caspase-3 activity by 20%, p53 protein level and the Bax/Bcl-2 ratio by 58 and 86%, respectively; increasing protein expression of the p-JAK2 and p-STAT3 by 26 and 156%, respectively, p-AKT protein level by 33%. The anti-apoptotic effects of sRAGE following I/R were blocked by JAK2 inhibitor AG 490. The effect of sRAGE reduction on TUNEL-positive myocytes and caspase-3 activity were abolished by PI3K inhibitor LY294002, but not ERK 1

  6. Experimental photoimmunology: immunologic ramifications of UV-induced carcinogenesis

    International Nuclear Information System (INIS)

    Daynes, R.A.; Bernhard, E.J.; Gurish, M.F.; Lynch, D.H.

    1981-01-01

    The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet light (UVL) exposure has clearly shown that the direct mutagenic effects of UVL is only one of the components involved in this process. In spite of the fact that overt carcinogenesis is only one of the many effects produced by UV light, most hypotheses as to the mechanism by which UVL can cause the mutations necessary to achieve the transformed phenotype have focused on the direct effects of UVL on DNA and the generation of carcinogenic compounds. Investigations during the last 5 yr, however, have clearly demonstrated that immunologic factors are also critically important in the pathogenesis of UV-induced skin cancers. A complete understanding of UV-carcinogenesis must therefore consider the mechanisms which allow the transformed cell to evade immunologic rejection by the host in addition to those aspects which deal with conversion of a normal cell to a cancer cell. It is the object of this review to provide both a historical account of the work which established the immunologic consequences of chronic UVL exposure and the results of recent experiments designed to investigate the kinetics and mechanisms by which UVL affects the immunologic apparatus. In addition, a hypothetical model is presented to explain the sequence of events which ultimately lead to the emergence of the suppressor T-cells which regulate antitumor immune responses

  7. Flagella-induced immunity against experimental cholera in adult rabbits.

    Science.gov (United States)

    Yancey, R J; Willis, D L; Berry, L J

    1979-07-01

    The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone.

  8. Electrical stimulation induces propagated colonic contractions in an experimental model.

    Science.gov (United States)

    Aellen, S; Wiesel, P H; Gardaz, J-P; Schlageter, V; Bertschi, M; Virag, N; Givel, J-C

    2009-02-01

    Direct colonic electrical stimulation may prove to be a treatment option for specific motility disorders such as chronic constipation. The aim of this study was to provoke colonic contractions using electrical stimulation delivered from a battery-operated device. Electrodes were inserted into the caecal seromuscular layer of eight anaesthetized pigs. Contractions were induced by a neurostimulator (Medtronic 3625). Caecal motility was measured simultaneously by video image analysis, manometry and a technique assessing colonic transit. Caecal contractions were generated using 8-10 V amplitude, 1000 micros pulse width, 120 Hz frequency for 10-30 s, with an intensity of 7-15 mA. The maximal contraction strength was observed after 20-25 s. Electrical stimulation was followed by a relaxation phase of 1.5-2 min during which contractions propagated orally and aborally over at least 10 cm. Spontaneous and stimulated caecal motility values were significantly different for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg respectively; P < 0.001, 42 experiments) and movement of contents (1.6(0.9) and 3.9(2.8) mm; P < 0.001, 40 experiments). Electrical stimulation modulated caecal motility, and provoked localized and propagated colonic contractions.

  9. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    International Nuclear Information System (INIS)

    Wang, W; Moriyama, L T; Bagnato, V S

    2013-01-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed. (review)

  10. Ventricular and myocardial scintiscanning: Methodical fundamentals

    International Nuclear Information System (INIS)

    Standke, R.; Hoer, G.; Maul, F.D.

    1984-01-01

    Nuclear cardiology is concerned with non invasive procedures to quantitate global and regional left ventricular function (Radionuclide ventriculography), also the imaging of vitally perfused myocardium (Myocardial scintigraphy) is achieved. A gammacamera and a minicomputer are necessary. Radionuclide ventriculography enables the analysis of global and regional time dependent left ventricular volume curves and hence the evaluation of contraction and contractility of the heart muscle. The basis is a sequence of scans covering an average heartcycle. This sequence may be produced either by first pass or equilibrium technique. Myocardial scintigraphy at rest images vital myocardium, scans immediately after exercise represent the interference of myocardial perfusion and muscle mass. The regional difference (Redistribution) between normalized exercise- and rest scans provide quantitative parameters to detect impairment of exercise-induced myocardial perfusion anomalies. The procedures of sectorial analysis of left ventricular function and myocardial perfusion are presented. (orig.) [de

  11. Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

    Science.gov (United States)

    Renard, E; Gaudin, A; Bienvenu, G; Amiaud, J; Farges, J C; Cuturi, M C; Moreau, A; Alliot-Licht, B

    2016-02-01

    Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria. © International & American

  12. Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis.

    Science.gov (United States)

    Barichello, Tatiana; Fagundes, Glauco D; Generoso, Jaqueline S; Dagostin, Caroline S; Simões, Lutiana R; Vilela, Márcia C; Comim, Clarissa M; Petronilho, Fabricia; Quevedo, João; Teixeira, Antonio L

    2014-01-01

    To evaluate the influence of environmental enrichment (EE) on memory, cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 × 10(6) CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood). EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.

  13. The potential role of amlodipine on experimentally induced bacterial rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    Full Text Available Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione and an oxidative product (malondialdehyde were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

  14. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (p ....02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p ....05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered...

  15. A Case of Acute ST-Segment Elevation Myocardial Infarction Mimicking Stress Induced Cardiomyopathy; Demonstration of Typical Echocardiographic Finding Correlated with Unusual Distribution of Left Anterior Descending Coronary Artery

    OpenAIRE

    Shin, Sung Kyun; Jin, Seon-Ah; Park, Yong Kyu; Park, Jae-Hyeong

    2010-01-01

    Stress-induced cardiomyopathy (SCMP) is diagnosed in 1-2% of patients presenting with symptoms suggestive of acute coronary syndrome. Because of sharing many common clinical features with SCMP, acute ST-segment elevation myocardial infarction (STEMI) can be misdiagnosed as SCMP. However, it can be associated with fatal outcome of the patient. Also, diagnosis of SCMP seems to be always challenging to clinicians, especially in the decision of taking coronary angiography which is still invasive ...

  16. Cytotoxicity induced by carbon nanotubes in experimental malignant glioma

    Directory of Open Access Journals (Sweden)

    Romano-Feinholz S

    2017-08-01

    Full Text Available Samuel Romano-Feinholz,1,* Alelí Salazar-Ramiro,2,* Emilio Muñoz-Sandoval,3 Roxana Magaña-Maldonado,2 Norma Hernández Pedro,4 Edgar Rangel López,5 Alberto González Aguilar,1 Aurora Sánchez García,6 Julio Sotelo,2 Verónica Pérez de la Cruz,7 Benjamín Pineda2 1Division of Neurosurgery, 2Neuroimmunology and Neuro-oncology Unit, National Institute of Neurology and Neurosurgery (NINN, Mexico City, 3Division of Advanced Materials, IPICYT, San Luis Potosí, 4Experimental Oncology Laboratory, National Cancer Institute of Mexico, 5Excitatory Aminoacids Laboratory, 6Pathology Laboratory, 7Neurochemistry Unit, National Institute of Neurology and Neurosurgery (NINN, Mexico City, Mexico *These authors contributed equally to this work Abstract: Despite multiple advances in the diagnosis of brain tumors, there is no effective treatment for glioblastoma. Multiwalled carbon nanotubes (MWCNTs, which were previously used as a diagnostic and drug delivery tool, have now been explored as a possible therapy against neoplasms. However, although the toxicity profile of nanotubes is dependent on the physicochemical characteristics of specific particles, there are no studies exploring how the effectivity of the carbon nanotubes (CNTs is affected by different methods of production. In this study, we characterize the structure and biocompatibility of four different types of MWCNTs in rat astrocytes and in RG2 glioma cells as well as the induction of cell lysis and possible additive effect of the combination of MWCNTs with temozolomide. We used undoped MWCNTs (labeled simply as MWCNTs and nitrogen-doped MWCNTs (labeled as N-MWCNTs. The average diameter of both pristine MWCNTs and pristine N-MWCNTs was ~22 and ~35 nm, respectively. In vitro and in vivo results suggested that these CNTs can be used as adjuvant therapy along with the standard treatment to increase the survival of rats implanted with malignant glioma. Keywords: carbon nanotubes, glioblastoma therapy

  17. THE EFFECT OF STRESS INDUCED-HYPERGLYCEMIA ON HOSPITAL TREATMENT OUTCOME IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH ST SEGMENT ELEVATION

    Directory of Open Access Journals (Sweden)

    Aleksandar Stojković

    2012-09-01

    Full Text Available Elevated glucose level on admission in the number of emergency conditions, including acute myocardial infarction (AMI, is linked to worse outcomes, regardless of the current treatment. The introduction of primary percutaneous coronary intervention (PPCI in therapy of AMI patients with ST segment elevation (STEMI has improved the treatment of these patients. However, there are contradictory evidences regarding the impact of stressinduced hyperglycemia on the treatment outcome. The present study is aimed to indentify the effect of stress-induced hyperglycemia on in-hospital prognosis of patients with STEMI treated with AIM-PPCI. Prospective study included 116 patients with a diagnosis of first AMI-STEMI treated with PPCI at the Department of Cardiovascular Diseases, Clinical Center Niš in the period 2010-2011. Immediately after establishing the diagnosis, the patients with adequate medicament preparation were transferred into the angiography room for the coronary stent implantation. Laboratory analysis of the whole blood samples were done immediately after admission and in the next 24 hours. Receiver operator characteristic (ROC analysis revealed that stress-induced hyperglycemia (glucose 11.2 mmol / L, an area under the curve of 0.812 is a delimiting factor for distinguishing the outcome and survival of patients on admission. The group of patients without stress-induced hyperglycemia had mortality rate about five times less (1/79 -1.2% than the group of patients with stress-induced hyperglycemia (5/37 -13.5%, p=0.041. Comparing these groups with the incidence of DM, stress-induced hyperglycemia had no significant effect on mortality in the group without DM (1/54 vs. 3/26, ns and in the group with DM (1/25 vs. 1/11, ns. The cut-off value of glucose, obtained by ROC curve, is 11.2 mmol/L for stressinduced hyperglycemia in patients with STEMI treated with PPCI. This value could determine a significant gradient of risk: patients with glycemia <11

  18. Early imaging of experimental myocardial infarction by intracoronary administration of /sup 131/I-labelled anticardiac myosin (Fab')/sub 2/ fragments. [Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Khaw, B.A.; Gold, H.K.; Leinbach, R.C.; Fallon, J.T.; Strauss, W.; Pohost, G.M.; Haber, E.

    1978-12-01

    The feasibility of early imaging of myocardial infarcts by intracoronary injection of /sup 131/I-labelled cardiac myosin-specific antibody (Fab')/sub 2/ was examined. The left anterior descending coronary artery was occluded for 5 hs by a balloon catheter introduced through the carotid artery in 12 dogs. The catheter was withdrawn and 1 mCi /sup 201/Tl was injected intravenously and 500 ..mu..Ci of /sup 131/I antibody were injected into the main left coronary artery. Six of these animals demonstrated evidence of myocardial infarction by ECG and subsequent triphenyl-tetrazolium chloride staining, while the others did not. In each of the infarcted animals, in vivo scintograms one-half h after injection of isotope showed uptake of /sup 131/I in the anteroapical region of the heart corresponding to the region of absent /sup 201/Tl uptake. This relationship was confirmed in the excized hearts and in heart slices. In slices, /sup 131/I uptake corresponded to regions that did not stain with triphenyltetrazolium chloride. In the six animals that did not show evidence for infarction after coronary occlusion, uptake of /sup 131/I was not demonstrated, either in vivo or in excized specimens. In four additional dogs subjected to the same procedure, /sup 125/I-labelled (Fab')/sub 2/ from nonimmune IgG was injected simultaneously into the left main coronary artery with /sup 131/I-labelled canine myosin-specific antibody (Fab')/sub 2/. The ratio of uptake between infarct center and normal tissue was 34.3 +- 1.5 (mean +- SEM) for the specific antibody fragment as contrasted to 6.6 +- 0.4 for the nonimmune IgG fragment, indicating that intracoronary injection does not favor nonspecific sequestration of protein in regions of infarction. Thus the intracoronary administration of myosin-specific antibody fragments leads to early and specific one-half h imaging of myocardial infarcts.

  19. Effect of Sechium edule on chemical induced kidney damage in experimental animals

    Directory of Open Access Journals (Sweden)

    Sayeed Mohammed Firdous Mumtaz

    2013-03-01

    Full Text Available The aqueous extract of leaves of Sechium edule was evaluated for its protective activity against gentamicin, potassium dichromate-induced nephrotoxicity and streptozotocin-induced diabetic nephropathy in experimental animals. In these three conditions, the extract of S. edule (200 mg/kg has significantly (p<0.001 decreased the level of blood urea, blood urea nitrogen and serum creatinine and also significantly (p<0.001 increased the serum levels of total protein. The serum uric acid level was also significantly (p<0.001 decrease in diabetic mice treated with the extract (200 mg/kg. The extract also improves the histology of the kidney. The results indicate that aqueous extract of leaves of S. edule has possessed protective effect against gentamicin- and potassium dichromate-induced nephrotoxicity and streptozotocin-induced diabetic nephropathy in experimental animals.

  20. [Protective effects of hypoxia-inducible factor-1 alpha on myocardial ischemia/reperfusion injury in rat and the role of protein kinase C in signal pathway].

    Science.gov (United States)

    Niu, Tie-sheng; Qi, Guo-xian; Fu, Peng; Sun, Ying-xian

    2010-02-01

    To study the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in a rat model of myocardial ischemia/reperfusion injury (IRI) and the role of protein kinase C (PKC) in signal pathway. A rat model of myocardial IRI was reproduced by 30 minutes of left anterior descending coronary artery (LCA) occlusion followed by 180 minutes of reperfusion. Thirty-two healthy male Wistar rats were randomly divided into four groups. The first group was ischemic preconditioning (IPC) group; the second group was simple IRI group; the third group was IPC plus PKC inhibitor group (IPC+I group); the fourth group was the sham-operation group without ligation of LCA. Eight rats were used in each group. The heart was harvested 180 minutes post-reperfusion, the mRNA and protein expression of HIF-1 alpha and heme oxygenase-1 (HO-1) were assessed. Meanwhile, the protein expression of caspase-3 was assayed. Blood samples were obtained from heart to determine the levels of interleukin-8 (IL-8) and myeloperoxidase (MPO). The mRNA and protein expression of HIF-1 alpha and HO-1 increased significantly in the IRI group compared with the sham-operation group, while the protein expression of caspase-3 increased significantly in the IRI group (HIF-1 alpha mRNA: 0.849+/-0.032 vs. 0.356+/-0.022, HIF-1 alpha protein: 0.762+/-0.042 vs. 0.324+/-0.016, HO-1 mRNA: 0.862+/-0.045 vs. 0.332+/-0.012, HO-1 protein: 0.792+/-0.044 vs. 0.335+/-0.031, caspase-3 protein: 0.371+/-0.015 vs. 0.061+/-0.012, respectively, all P<0.01). The levels of IL-8 and MPO increased significantly in the IRI group [IL-8: (812+/-26) ng/L vs. (72+/-13) ng/L, MPO: (78.7+/-2.9) kU/L vs. (13.3+/-1.5) kU/L, both P<0.01]. The protein and mRNA expression of HIF-1 alpha and HO-1 increased significantly in the IPC group compared with IRI group (HIF-1 alpha mRNA: 1.412+/-0.039, HIF-1 alpha protein: 1.362+/-0.045, HO-1 mRNA: 1.523+/-0.038, HO-1 protein: 1.420+/-0.041, respectively), meanwhile the protein expression of caspase-3 (0

  1. Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study

    OpenAIRE

    Abdelaleem, Shereen Abdelhakim; Hassan, Osama A.; Ahmed, Rasha F.; Zenhom, Nagwa M.; Rifaai, Rehab A.; El-Tahawy, Nashwa F.

    2017-01-01

    Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this ...

  2. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Jørgensen, Erik; Wang, Yongzhong

    2006-01-01

    BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy......: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group....... measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups. CONCLUSIONS...

  3. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction the prevale...

  4. Histometric assessment of the effect of diabetes mellitus on experimentally induced periodontitis in rats.

    Science.gov (United States)

    Pepelassi, Eudoxie; Xynogala, Ioanna; Perrea, Despina; Agrogiannis, George; Pantopoulou, Alkistis; Patsouris, Efstratios; Vrotsos, Ioannis

    2012-04-01

    The aim of this interventional animal study was to assess histologically the effect of experimental diabetes in rats with experimental periodontitis in terms of alveolar bone loss and the effect of experimental periodontitis on glucose levels in diabetes. Forty-seven Wistar rats were studied: 12 healthy controls (C), 10 with experimental diabetes (D), 12 with experimental diabetes and experimental periodontitis (DP) and 13 with experimental periodontitis (P). Diabetes was induced by streptozotocin injection and periodontitis was induced at the right second maxillary molar by ligation. Serum glucose levels were measured at specific time points. Sixty-one days after ligation, the rats were sacrificed. Histometric analysis assessed alveolar crest level. For ligated groups, alveolar bone loss was expressed as the difference in alveolar crest level between right and left maxillary molars. Diabetes alone did not statistically significantly affect alveolar crest level. The combination of diabetes and periodontitis caused greater alveolar bone loss (946.1 +/- 719.9 microm) than periodontitis alone (639.7 +/- 294.2 microm); however, the difference did not reach statistical significance. Periodontitis did not significantly increase glucose levels in diabetic rats. The average glucose levels were 545.4 (499 - 563) and 504.5 (445 - 560) mg/dL for diabetic and diabetic ligated rats, respectively. Within its limits, this study demonstrated that the severity of alveolar bone loss in periodontitis was not significantly aggravated by diabetes and the serum glucose levels in diabetes were not affected by periodontitis.

  5. Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling.

    Science.gov (United States)

    Antonopoulos, Alexios S; Margaritis, Marios; Verheule, Sander; Recalde, Alice; Sanna, Fabio; Herdman, Laura; Psarros, Costas; Nasrallah, Hussein; Coutinho, Patricia; Akoumianakis, Ioannis; Brewer, Alison C; Sayeed, Rana; Krasopoulos, George; Petrou, Mario; Tarun, Akansha; Tousoulis, Dimitris; Shah, Ajay M; Casadei, Barbara; Channon, Keith M; Antoniades, Charalambos

    2016-03-04

    Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase-derived O2 (-), whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2 (-). In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase-mediated translocation of Rac1 and p47(phox) from the cytosol to the membranes. Induction of O2 (-) production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ-mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ-mediated upregulation of ADIPOQ in EpAT. We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress. © 2016 The Authors.

  6. Classification of myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Hosbond, Susanne

    2013-01-01

    The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand...

  7. Crise de feocromocitoma simulando um infarto agudo do miocárdio em paciente com artérias coronárias normais Pheochromocytoma-induced segmental myocardial dysfunction mimicking an acute myocardial infarction in a patient with normal coronary arteries

    Directory of Open Access Journals (Sweden)

    Eduardo S. Darzé

    2004-02-01

    Full Text Available Relatamos o caso de um paciente com alterações eletrocardiográficas e disfunção miocárdica segmentar induzidas por feocromocitoma, simulando infarto agudo do miocárdio. A angiografia coronariana foi normal e houve normalização completa do eletrocardiograma e ecocardiograma, após terapia com um bloqueador alfa-adrenérgico e ressecção do tumor. Espasmo coronariano foi o provável mecanismo envolvido na produção dessas alterações, ilustrando a importância de manter um alto grau de suspeição clínica em pacientes com evento miocárdico inesperado em meio a uma crise hipertensiva.We report a case of pheochromocytoma-induced segmental myocardial dysfunction and electrocardiographic abnormalities mimicking an acute anterior myocardial infarction, probably due to coronary spasm. Coronary angiography showed normal coronaries, and the electrocardiographic and echocardiographic changes resolved completely after therapy with an alpha-adrenergic blocker and tumor removal. Our case illustrates the importance of maintaining a high index of suspicion in patients presenting with an unexpected myocardial event and a hypertensive crisis.

  8. Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in Patients with ST-Elevation Myocardial Infarction

    DEFF Research Database (Denmark)

    Ekeloef, Sarah; Halladin, Natalie; Fonnes, Siv

    2017-01-01

    Melatonin has attenuated myocardial ischemia reperfusion injury in experimental studies. We hypothesized that the administration of melatonin during acute myocardial reperfusion improves myocardial salvage index in patients with ST-elevation myocardial infarction. Patients (n = 48) were randomized...... in a 1:1 ratio to intracoronary and intravenous melatonin (total 50 mg) or placebo. The myocardial salvage index assessed by cardiac magnetic resonance imaging at day 4 (± 1 day) after primary percutaneous coronary intervention was similar in the melatonin group (n = 22) at 55.3% (95% CI 47...... did not differ between the groups. In conclusion, melatonin did not improve the myocardial salvage index after primary percutaneous coronary intervention in patients with ST elevation myocardial infarction compared with placebo....

  9. Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch.

    Directory of Open Access Journals (Sweden)

    Alexandru D P Papoiu

    2011-03-01

    Full Text Available Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS.In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases. Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001.Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans.

  10. Experimental and numerical study of wave-induced backfilling beneath submarine pipelines

    DEFF Research Database (Denmark)

    Bayraktar, Deniz; Ahmad, Joseph; Eltard-Larsen, Bjarke

    2016-01-01

    This paper presents results of complementary experimental and numerical studies involving wave-induced backfilling of current-generated scour holes beneath submarine pipelines. The laboratory experiments are conducted in a wave-plus-current flume, utilizing Laser Doppler Anemometry to measure...

  11. Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities

    NARCIS (Netherlands)

    Brand, H. S.; Maas, M. A.; Bosma, A.; van Ketel, R. J.; Speelman, P.; Chamuleau, R. A.

    1994-01-01

    In three experimental models in rats, surgical construction of a self-filling blind loop (SFBL), trinitrobenzene sulfonic acid (TNB) -induced colitis, and the combination of SFBL and TNB, the hypothesis was studied that intestine-derived endotoxins play a role in the pathogenesis of hepatobiliary

  12. Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Tran, E H; Hardin-Pouzet, H; Verge, G

    1997-01-01

    Nitric oxide (NO), produced by inducible NO synthase (iNOS), may play a role in inflammatory demyelinating diseases of the central nervous system (CNS). We show upregulation of iNOS mRNA in CNS of SJL/J mice with experimental allergic encephalomyelitis (EAE). Using antibodies against mouse i...

  13. Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish

    DEFF Research Database (Denmark)

    Haarder, Simon; Kania, Per Walter; Holm, Thomas

    2017-01-01

    with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated...

  14. Physical and Clinical Pathological Findings Associated with Experimentally Induced Rupture of the Equine Urinary Bladder

    OpenAIRE

    Genetzky, Roger M.; Hagemoser, Wayne A.

    1985-01-01

    Two mature horses were examined for changes in laboratory and physical findings after experimentally induced bladder rupture. The postrupture laboratory diagnostic changes, which provide valuable information for a correct diagnosis are described. Hematology, serum and peritoneal fluid sodium, potassium, calcium, phosphorous, creatinine, urea nitrogen, albumin and peritoneal fluid components were measured and evaluated versus time. Hyponatremia and hyperkalemia occurred, as well as increased c...

  15. Status of experimental data of proton-induced reactions for intermediate-energy nuclear data evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yukinobu; Kawano, Toshihiko [Kyushu Univ., Fukuoka (Japan); Yamano, Naoki; Fukahori, Tokio

    1998-11-01

    The present status of experimental data of proton-induced reactions is reviewed, with particular attention to total reaction cross section, elastic and inelastic scattering cross section, double-differential particle production cross section, isotope production cross section, and activation cross section. (author)

  16. Experimental Study on Piezoelectric Energy Harvesting from Vortex-Induced Vibrations and Wake-Induced Vibrations

    Directory of Open Access Journals (Sweden)

    Min Zhang

    2016-01-01

    Full Text Available A rigid circular cylinder with two piezoelectric beams attached on has been tested through vortex-induced vibrations (VIV and wake-induced vibrations (WIV by installing a big cylinder fixed upstream, in order to study the influence of the different flow-induced vibrations (FIV types. The VIV test shows that the output voltage increases with the increases of load resistance; an optimal load resistance exists for the maximum output power. The WIV test shows that the vibration of the small cylinder is controlled by the vortex frequency of the large one. There is an optimal gap of the cylinders that can obtain the maximum output voltage and power. For a same energy harvesting device, WIV has higher power generation capacity; then the piezoelectric output characteristics can be effectively improved.

  17. Myocardial Na,K-ATPase: Clinical aspects

    Science.gov (United States)

    Kjeldsen, Keld

    2003-01-01

    The specific binding of digitalis glycosides to Na,K-ATPase is used as a tool for Na,K-ATPase quantification with high accuracy and precision. In myocardial biopsies from patients with heart failure, total Na,K-ATPase concentration is decreased by around 40%; a correlation exists between a decrease in heart function and a decrease in Na,K-ATPase concentration. During digitalization, around 30% of remaining pumps are occupied by digoxin. Myocardial Na,K-ATPase is also influenced by other drugs used for the treatment of heart failure. Thus, potassium loss during diuretic therapy has been found to reduce myocardial Na,K-ATPase, whereas angiotensin-converting enzyme inhibitors may stimulate Na,K pump activity. Furthermore, hyperaldosteronism induced by heart failure has been found to decrease Na,K-ATPase activity. Accordingly, treatment with the aldosterone antagonist, spironolactone, may also influence Na,K-ATPase activity. The importance of Na,K pump modulation with heart disease, inhibition in digitalization and other effects of medication should be considered in the context of sodium, potassium and calcium regulation. It is recommended that digoxin be administered to heart failure patients who, after institution of mortality-reducing therapy, still have heart failure symptoms, and that the therapy be continued if symptoms are revealed or reduced. Digitalis glycosides are the only safe inotropic drugs for oral use that improve hemodynamics in heart failure. An important aspect of myocardial Na,K pump affection in heart disease is its influence on extracellular potassium (Ke) homeostasis. Two important aspects should be considered: potassium handling among myocytes, and effects of potassium entering the extracellular space of the heart via the bloodstream. It should be noted that both of these aspects of Ke homeostasis are affected by regulatory aspects, eg, regulation of the Na,K pump by physiological and pathophysiological conditions, as well as by medical

  18. Exercise Training Protects Against Acute Myocardial Infarction via Improving Myocardial Energy Metabolism and Mitochondrial Biogenesis.

    Science.gov (United States)

    Tao, Lichan; Bei, Yihua; Lin, Shenghui; Zhang, Haifeng; Zhou, Yanli; Jiang, Jingfa; Chen, Ping; Shen, Shutong; Xiao, Junjie; Li, Xinli

    2015-01-01

    Acute myocardial infarction (AMI) represents a major cause of morbidity and mortality worldwide. Exercise has been proved to reduce myocardial ischemia-reperfusion (I/R) injury However it remains unclear whether, and (if so) how, exercise could protect against AMI. Mice were trained using a 3-week swimming protocol, and then subjected to left coronary artery (LCA) ligation, and finally sacrificed 24 h after AMI. Myocardial infarct size was examined with triphenyltetrazolium chloride staining. Cardiac apoptosis was determined by TUNEL staining. Mitochondria density was checked by Mito-Tracker immunofluorescent staining. Quantitative reverse transcription polymerase chain reactions and Western blotting were used to determine genes related to apoptosis, autophagy and myocardial energy metabolism. Exercise training reduces myocardial infarct size and abolishes AMI-induced autophagy and apoptosis. AMI leads to a shift from fatty acid to glucose metabolism in the myocardium with a downregulation of PPAR-α and PPAR-γ. Also, AMI induces an adaptive increase of mitochondrial DNA replication and transcription in the acute phase of MI, accompanied by an activation of PGC-1α signaling. Exercise abolishes the derangement of myocardial glucose and lipid metabolism and further enhances the adaptive increase of mitochondrial biogenesis. Exercise training protects against AMI-induced acute cardiac injury through improving myocardial energy metabolism and enhancing the early adaptive change of mitochondrial biogenesis. © 2015 S. Karger AG, Basel.

  19. Exercise Training Protects Against Acute Myocardial Infarction via Improving Myocardial Energy Metabolism and Mitochondrial Biogenesis

    Directory of Open Access Journals (Sweden)

    Lichan Tao

    2015-08-01

    Full Text Available Background/Aims: Acute myocardial infarction (AMI represents a major cause of morbidity and mortality worldwide. Exercise has been proved to reduce myocardial ischemia-reperfusion (I/R injury However it remains unclear whether, and (if so how, exercise could protect against AMI. Methods: Mice were trained using a 3-week swimming protocol, and then subjected to left coronary artery (LCA ligation, and finally sacrificed 24 h after AMI. Myocardial infarct size was examined with triphenyltetrazolium chloride staining. Cardiac apoptosis was determined by TUNEL staining. Mitochondria density was checked by Mito-Tracker immunofluorescent staining. Quantitative reverse transcription polymerase chain reactions and Western blotting were used to determine genes related to apoptosis, autophagy and myocardial energy metabolism. Results: Exercise training reduces myocardial infarct size and abolishes AMI-induced autophagy and apoptosis. AMI leads to a shift from fatty acid to glucose metabolism in the myocardium with a downregulation of PPAR-α and PPAR-γ. Also, AMI induces an adaptive increase of mitochondrial DNA replication and transcription in the acute phase of MI, accompanied by an activation of PGC-1α signaling. Exercise abolishes the derangement of myocardial glucose and lipid metabolism and further enhances the adaptive increase of mitochondrial biogenesis. Conclusion: Exercise training protects against AMI-induced acute cardiac injury through improving myocardial energy metabolism and enhancing the early adaptive change of mitochondrial biogenesis.

  20. Experimental and Theoretical Investigation of Shock-Induced Reactions in Energetic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Jeffrey J. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Park, Samuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kohl, Ian Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Knepper, Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Farrow, Darcie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tappan, Alexander S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    In this work, shock-induced reactions in high explosives and their chemical mechanisms were investigated using state-of-the-art experimental and theoretical techniques. Experimentally, ultrafast shock interrogation (USI, an ultrafast interferometry technique) and ultrafast absorption spectroscopy were used to interrogate shock compression and initiation of reaction on the picosecond timescale. The experiments yielded important new data that appear to indicate reaction of high explosives on the timescale of tens of picoseconds in response to shock compression, potentially setting new upper limits on the timescale of reaction. Theoretically, chemical mechanisms of shock-induced reactions were investigated using density functional theory. The calculations generated important insights regarding the ability of several hypothesized mechanisms to account for shock-induced reactions in explosive materials. The results of this work constitute significant advances in our understanding of the fundamental chemical reaction mechanisms that control explosive sensitivity and initiation of detonation.

  1. Myocardial imaging. Coxsackie myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  2. Myocardial imaging. Coxsackie myocarditis

    International Nuclear Information System (INIS)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-01-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1

  3. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium.

    Science.gov (United States)

    Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel

    2014-03-28

    Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament.

  4. Comparison of electrocardiography and thallium-201 myocardial scintigraphy for the detection of ergonovine-induced coronary artery spasm: angiographic correlation

    International Nuclear Information System (INIS)

    Shanes, J.G.; Pavel, D.; Blend, M.

    1987-01-01

    This study was performed to determine the sensitivity of thallium imaging vs ECG monitoring for detecting coronary artery spasm noninvasively following intravenous ergonovine administration as compared to simultaneous coronary angiography. Thirty-two patients with insignificant coronary artery disease and chest pain underwent 12-lead ECG monitoring, thallium imaging, and coronary arteriography following the administration of 0.05, 0.1, 0.2, and 0.3 mg of ergonovine given 5 minutes apart or until chest pain occurred. One minute following the last dose of ergonovine, 2.5 mCi of thallium-201 was injected intravenously, and a final ECG was recorded and repeat coronary arteriography performed. Within 10 minutes following the injection of thallium, imaging was performed in the 40-degree and 70-degree left anterior oblique and anterior projections. The ECG, thallium study, and coronary arteriogram were read blindly and results were compared. The ECG, angiogram, and thallium study were read as positive if the following occurred, respectively: greater than or equal to 1 mm ST segment elevation, depression, or T wave reversal; greater than 50% vessel narrowing,; and reversible perfusion defect. Five patients were excluded from analysis because of either catheter-induced spasm, suboptimal thallium studies, or protocol violations. Of the 27 patients included for analysis, six had chest pain, five had a positive angiogram, five had a positive thallium study, and one had a positive ECG. The sensitivity of thallium vs ECG monitoring was 80% vs 25%, and the accuracy was 92% vs 80%. We conclude that thallium imaging greatly increases the noninvasive detection of ergonovine-induced coronary spasm as compared with the ECG with no loss of accuracy

  5. The effect of preferred music genre selection versus preferred song selection on experimentally induced anxiety levels.

    Science.gov (United States)

    Walworth, Darcy DeLoach

    2003-01-01

    The purpose of this study was to investigate the differences of experimentally induced anxiety levels reached by subjects listening to no music (n = 30), subjects listening to music selected by the experimenter from the subject's preferred genre or artist listed as relaxing (n = 30), and subjects listening to a specific song they listed as relaxing (n = 30). Subjects consisted of 90 individuals, male and female, randomly assigned to one of the three groups mentioned above. Subjects in either music group filled out a questionnaire prior to participating in the study indicating their preference of music used for relaxation purposes. Subjects in Experimental Group 1 marked their preferred genres and/or artists, and Experimental Group 2 marked specific songs used for relaxation purposes. While the experimenter hypothesized subjects in Experimental Group 2 would show less anxiety than both the control group and Experimental Group 1, there were no significant differences found between the 2 music groups in anxiety levels reached. However, there was a statistically significant difference between the no music control group and both music groups in the anxiety level reached by subjects. Subjects listening to music, both songs chosen by the experimenter and subject selected songs, showed significantly less anxiety than subjects not listening to music.

  6. Anesthetic-Induced Myocardial Preconditioning and Some Biochemical Markers for Cardiac and Coronary Failures after Aortocoronary Bypass Surgery

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2013-01-01

    Full Text Available Objective: to provide a rationale for the efficiency of sevoflurane-induced cardiac preconditioning (CPC, by assessing the pattern of recovery of heart rate and by estimating troponin I levels and changes in NT-proBNP concentrations in patients undergoing aortocoronary bypass surgery (ACBS under extracorporeal circulation (EC. Subjects and methods. Sixty patients aged 60.6±8 years (M±& were examined after elective ACBS using EC and divided into two groups of 30 patients each: 1 inhalation induction and maintenance of anesthesia (IIMA with sevoflurane and fentanyl, with CPC being simulated; 2 total intravenous anesthesia (TIA with propofol and fentanyl. Inhalation induction of sevoflurane anesthesia was performed in the IIMA group. Ten minutes before aortic ligation, the dose of the anesthetic was increased up to 2 MAC for CPC. Inhaled anesthetics were not used in the TIA group. The authors assessed the pattern of cardiac performance recovery and estimated the level of NT-proBNP 24 and 48 hours after tracheal intubation and that of troponin I following 24 hours of the intubation. Results. Defibrillation was required in one patient from the TIA group who developed ventricular fibrillation. The baseline levels of NT-proBNP were comparable in both groups. Following 24 hours, its level was more than thrice higher in the TIA group than that in the IIMA one (p<0.05. By the end of 2 days, the concentration of NT-proBNP continued to rise (up to 480% of the baseline level in the TIA group and returned to the preoperative values in the IIMA group (p=0.05. Twenty-four hours after tracheal intubation the level of troponin I was insignificantly higher in the TIA group than that in the IIMA group (p=0.1. Conclusion. Sevoflurane has cardioprotective properties in preventing and/or reducing the degree of heart failure after ACBS using EC. There is a need to continue the study in increased cohort to provide evidence that sevoflurane-induced CPC can lower

  7. Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis.

    Directory of Open Access Journals (Sweden)

    Sara Tengvall

    Full Text Available Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA. Targeting the expression of the collagen type II (CII to antigen presenting cells (APCs induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1 increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.

  8. Myocardial Rac1 exhibits partial involvement in thyroxin-induced cardiomyocyte hypertrophy and its inhibition is not sufficient to improve cardiac dysfunction or contractile abnormalities in mouse papillary muscles.

    Science.gov (United States)

    Elnakish, Mohammad T; Moldovan, Leni; Khan, Mahmood; Hassanain, Hamdy H; Janssen, Paul M L

    2013-06-01

    : Development of cardiac hypertrophy after thyroxin (T4) treatment is well recognized. Recently, we observed that T4-induced cardiac hypertrophy is associated with increased cardiac Rac1 expression and activity. Whether this Rac1 increase has a role in inducing this cardiac phenotype is, however, still unknown. Here, we showed that T4 treatment (500 µg/kg/d) for 2 weeks resulted in increased myocardial Rac1 activity with subsequent hypertension, cardiac hypertrophy, and left ventricular systolic dysfunction in vivo. Isolated right ventricular papillary muscles of T4-treated mice maintained their peak isometric active developed tension but exhibited significant decreases in their corresponding time to peak and in relaxation times. Positive inotropic responses to increasing pacing rate and β-adrenergic stimulation were also depressed in these muscles. Pravastatin (10 mg/kg/d), a Rac1 inhibitor, significantly decreased myocardial Rac1 activity, hypertension, and cardiomyocyte size in T4-treated mice but could not attenuate gross heart weight or functional cardiac changes in these mice. Our data showed that T4 could activate different signaling pathways with distinct cardiovascular outcomes. We also provide the first mechanistic evidence for the partial involvement of Rac1 activation in T4-induced cardiomyocyte hypertrophy and reveal a putative role for Rac1 in the development of T4-induced hypertension.

  9. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  10. Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

    Science.gov (United States)

    Lavezzo, A; Melillo, G; Clavenna, G; Omini, C

    1992-06-01

    The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough.

  11. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

    Science.gov (United States)

    Fernandez, Diego C; Pasquini, Laura A; Dorfman, Damián; Aldana Marcos, Hernán J; Rosenstein, Ruth E

    2012-01-01

    Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  12. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

    Directory of Open Access Journals (Sweden)

    Diego C Fernandez

    Full Text Available Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  13. Experimental gingivitis induces systemic inflammatory markers in young healthy individuals: a single-subject interventional study.

    Science.gov (United States)

    Eberhard, Jörg; Grote, Karsten; Luchtefeld, Maren; Heuer, Wieland; Schuett, Harald; Divchev, Dimitar; Scherer, Ralph; Schmitz-Streit, Ruth; Langfeldt, Daniela; Stumpp, Nico; Staufenbiel, Ingmar; Schieffer, Bernhard; Stiesch, Meike

    2013-01-01

    We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development. Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown. 37 non-smoking young volunteers with no inflammatory disease or any cardiovascular risk factors participated in this single-subject interventional study with an intra-individual control. Intentionally experimental oral inflammation was induced by the interruption of oral hygiene for 21 days, followed by a 21-days resolving phase after reinitiation of oral hygiene. Primary outcome measures at baseline, day 21 and 42 were concentrations of hsCRP, IL-6, and MCP-1, as well as adhesion capacity and oxLDL uptake of isolated blood monocytes. The partial cessation of oral hygiene procedures was followed by the significant increase of gingival bleeding (34.0%, Pgingivitis. Bacterial-induced gingival low-level inflammation induced a systemic increase in inflammatory markers. Dental hygiene almost completely reversed this experimental inflammatory process, suggesting that appropriate dental prophylaxis may also limit systemic markers of inflammation in subjects with natural gingivitis. International Clinical Trials Register Platform of the World Health Organization, registry number: DRKS00003366, URL: http://apps.who.int/trialsearch/Default.aspx.

  14. The Pathogenesis of Human Myocardial Infarction

    Science.gov (United States)

    Rona, George

    1966-01-01

    Coronary arteriography, dissection of the coronary arteries and histopathological examination of the heart were carried out in 150 autopsies to study the effect of coronary narrowing and occlusion, of the presence of collaterals, and of coronary artery predominance on the development of myocardial infarction. The thrombosis rate was related to the severity of coronary sclerosis. The development of collaterals was not enhanced by coronary sclerosis and occlusion, and collaterals did not protect the myocardium against reinfarction. Coronary occlusion was regularly demonstrable in recent myocardial infarct cases. The association of atrial and posterior ventricular infarcts was explained by occlusion of their common arterial branch. The interdependence between coronary sclerosis, thrombosis and myocardial infarction in human autopsy material emphasizes the importance of mural coronary artery disease in the genesis of coronary occlusion and myocardial infarction, and it is at variance with statistical data and experimental results. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:5924947

  15. [Blood serum lipoprotein spectrum in myocardial infarct].

    Science.gov (United States)

    Efremushkin, G G; Goriacheva, A V; Kolomenskaia, T I; Solomatina, L G; Ovcharenko, R P

    1979-11-01

    The lipoprotein spectrum was studied in polyacrylamide gel and by thin-layer chromatography on silica gel in 236 patients with myocardial infarction in different periods of the disease, in 45 patients with unstable angina pectoris, in 75 healthy persons and in 8 dogs with experimental myocardial infarction. Besides an increase in the concentration of cholesterol and triglycerides and a decrease in the level of diglycerides in blood serum, there is a disturbance in the ratio of phospholipid fractions, mainly in myocardial infarction. The level of pre-beta-lipoproteins was increased in the acute period of myocardial infarction, the level of beta-lipoproteins in the subacute period. Complications and concomitant inflammatory diseases were attended by a higher level of beta-lipoproteins. A connection was noted between the lipoprotein spectrum, predominantly of the pre-beta-fraction, and the ABO phenotype and the season.

  16. Rat experimental model of myocardial ischemia/reperfusion injury: an ethical approach to set up the analgesic management of acute post-surgical pain.

    Directory of Open Access Journals (Sweden)

    Maria Chiara Ciuffreda

    Full Text Available RATIONALE: During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R's ethic principles, in particular the principle of Reduction. METHODS: Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal, or carprofen (5 mg/kg sub-cutaneous, or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group. We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery. RESULTS: Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05 and the second hour (43±21 vs 74±24; p<0.05 post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05. Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05. Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05. CONCLUSIONS: Multi-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after

  17. Microbiological profile and calprotectin expression in naturally occurring and experimentally induced gingivitis.

    Science.gov (United States)

    Farina, Roberto; Guarnelli, Maria Elena; Figuero, Elena; Herrera, David; Sanz, Mariano; Trombelli, Leonardo

    2012-10-01

    This study was performed to evaluate the microbiological profile and the calprotectin expression in gingival crevicular fluid (GCF) in spontaneous and experimentally induced gingival inflammation. Thirty-seven periodontally healthy subjects were evaluated in real life conditions (N-O gingivitis) as well as after 21 days of experimental gingivitis trial (E-I gingivitis). During the experimental gingivitis trial, in one maxillary quadrant (test quadrant), gingival inflammation was induced by oral hygiene abstention, while in the contralateral (control) quadrant, oral hygiene was routinely continued. The results of the study showed that (1) the microbiological profile of quadrants where gingival inflammation was experimentally induced (i.e., E-I test quadrants) differed significantly from that of either quadrants where gingival inflammation was controlled by proper plaque control (i.e., E-I control quadrants) or quadrants with N-O gingivitis, and (2) GCF calprotectin was significantly higher at E-I test quadrants compared to either E-I control quadrants or quadrants with N-O gingivitis. A positive intrasubject correlation was found between GCF concentration of calprotectin at sites presenting N-O and E-I gingivitis. N-O and E-I gingivitis showed a different microbiological profile of the subgingival environment. GCF calprotectin is a reliable marker of gingival inflammation, and its concentration in N-O gingivitis is correlated with its expression in E-I gingivitis. The modality of plaque accumulation seems to affect the subgingival microbiological profile associated with a gingivitis condition. Calprotectin levels in GCF may be regarded as a promising marker of the individual susceptibility to develop gingival inflammation in response to experimentally induced plaque accumulation.

  18. Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS-mediated PI3K/Akt/mTOR pathway in vitro and in vivo.

    Science.gov (United States)

    Chen, Lvyi; Liu, Peng; Feng, Xin; Ma, Chunhua

    2017-12-01

    The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)-induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase (CK), lactate dehydrogenase, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), glutathione, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured after the rats were killed. iNOS, COX-2, NF-κB and PI3K/Akt/mTOR pathway proteins were detected by Western blot. In vitro, we evaluated the protective effect of Sal on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Reactive oxygen species (ROS) in H9c2 cells was measured by flow cytometry, and the activities of the antioxidant enzymes CAT, SOD, GSH-px, glutathione-S-transferase, TNF-α, IL-6 and IL-1β in cellular supernatant were measured. PI3K/Akt/mTOR signalling was examined by Western blot. As a result, Sal significantly attenuated the above indices. In addition, Sal exerts pronounced cardioprotective effect in rats subjected to LPS possibly through inhibiting the iNOS, COX-2, NF-κB and PI3K/Akt/mTOR pathway in vivo. Furthermore, the pharmacological effect of Sal associated with the ROS-mediated PI3K/Akt/mTOR pathway was proved by the use of ROS scavenger, N-acetyl-l-cysteine, in LPS-stimulated H9C2 cells. Our results indicated that Sal could be a potential therapeutic agent for the treatment of cardiovascular disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  19. Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Leonardo Bocchi

    Full Text Available Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI, lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60 or vehicle (V, n = 55, or sham operated (n = 18. In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration

  20. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  1. Noninvasive detection of coronary artery disease by myocardial imaging with thallium-201

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Usami, Masahisa

    1981-01-01

    Dipyridamole-loading myocardial imaging was performed in 38 patients with coronary artery diseases(CAD). The diagnostic accuracy of this method was 66%. The combination of dipyridamole-loading and exercise stress myocardial imaging increased the diagnostic sensitivity of CAD from 71% (exercise stress imaging only) to 87%. In addition, dipyridamole-loading myocardial imaging was useful for the diagnosis of CAD in patients who could not perform exercise stree test. Chest pain and ST-segment depression were induced less often during dipyridamole administration than exercise stress test. Animal experiments showed that dipyridamole caused abnormalities in myocardial blood flow and myocardial Tl uptake distal to the critical coronary stenosis. And dipyridamole increased myocardial blood flow by 142% and myocardial Tl concentration by 62% in the normally perfused myocardial segments. Ergonovine-loading myocardial imaging was performed in 8 patients with resting angina and without significant coronary stenosis. And in all of them, ergonivine induced cold-spots on myocardial imaging with or without chest pain and ST-segment shift. Ergonovine-loading myocardial imaging was useful for the diagnosis of angina induced by coronary artery spasm. The combination of initial and delayed resting myocardial imaging was useful to differentiate the underperfused but viable myocardium from the scar. And by comparing with radionuclide angiography obtained before and after nitroglycerin(NTG) administration, ATG-loading myocardial imaging and electrocardiogram(ECG) findings in 20 patients with CAD, we demonstrated that the transient defective myocadial segments were underperfused but viable. (author)

  2. Diagnostic value of combining heart rate recovery and P-wave changes with exercise-induced changes in the ST segments for prediction of myocardial ischaemia.

    Science.gov (United States)

    Koyuncu, Ilhan; Tuluce, Kamil; Tuluce, Selcen Yakar; Koyuncu, Betul; Eyuboglu, Mehmet; Eyopoglu, Mehmet; Gursul, Erdal; Akcay, Filiz Akyildiz; Safak, Ozgen; Ekinci, Mehmet Akif; Ozdogan, Ozhan; Kozan, Omer

    2015-08-01

    In patients admitted to outpatient clinics with chest pain, changes in the ST-segments of electrocardiogram (ECG) readings are the most widely used criteria during treadmill ECG tests to determine myocardial ischaemia, despite its poor accuracy. In this study, we evaluated the benefit of combining elongation of P-wave duration (Pdur) and abnormal heart rate recovery (HRR) parameters in addition to changes in the ST-segments for the detection of myocardial ischaemia with treadmill ECG testing. Patients (n = 369) with chest pain who underwent both a treadmill ECG test and myocardial perfusion scintigraphy (MPS) were enrolled. P-wave duration was measured at rest and at the end of the first minute of the recovery phase and elongation of the P-wave was calculated. Abnormal HRR was defined as the failure of a decreasing HR at the end of the first minute of the recovery phase >10% of the maximum HR reached during treadmill ECG testing. The sensitivity, specificity, positive and negative predictive values, diagnostic accuracy values, and likelihood ratios (LRs) of changes in the ST-segments, P-wave elongation, abnormal HRR, and the combination of these three variables for predicting myocardial ischaemia detected by MPS, were calculated separately-in patients without previous coronary artery disease (CAD) and in those with CAD. Elongation of Pdur by 20 ms or longer and abnormal HRR during treadmill ECG test were more common in patients with reversible perfusion defects in MPS than in those without perfusion defects (both P predictive value, 88.9% positive predictive value, and 70% diagnostic accuracy in 77 patients with previous CAD. The LR+ of the combination of the three variables was 12.27. The addition of elongation of Pdur 20 ms and abnormal HRR to the development of significant changes in the ST-segments detected myocardial ischaemia with 52.7% sensitivity, 98.7% specificity, 89.9% negative predictive value, 90.6% positive predictive value, and 90% diagnostic

  3. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    use

    2011-11-16

    Nov 16, 2011 ... good experimental materials for regenerative medicine and drug testing to enhance research results in the future. Key words: Myocardial ... mechanisms for myocardial repair and regeneration. (Minguell and Erices, 2006). ... macrophages phagocytose the necrotic cell debris and lead to the subsequent ...

  4. Tenascin and fibronectin expression in healing human myocardial scars

    NARCIS (Netherlands)

    Willems, I. E.; Arends, J. W.; Daemen, M. J.

    1996-01-01

    Fibronectin and tenascin are matrix proteins known to be present in early experimental wound healing. As only limited data are available regarding early matrix changes in human myocardial infarction, the presence of tenascin and fibronectin was studied in human myocardial infarctions of different

  5. Trust and Cheating in Sri Lanka: The Role of Experimentally-Induced Emotions about Tsunam

    OpenAIRE

    Pierluigi Conzo

    2014-01-01

    Through a field experiment in Sri Lanka I analyze the role of experimentally-induced memories of 2004 tsunami on behavior in a trust game in which personal notions of cheating are elicited. Microfinance borrowers were randomly assigned to a treatment (control) group consisting in watching a video about the calamity before (after) playing. Trust game participants were asked how much to receive (return) in order not to (make the counterpart) feel cheated; in a survey they selected whether the v...

  6. Experimental study of corrosion-induced degradation of reinforced concrete elements

    OpenAIRE

    LOUKIL, Olfa; Adelaide, Lucas; Bouteiller, Véronique; Quiertant, Marc; Chaussadent, Thierry; Ragueneau, Frédéric; Bourbon, Xavier; Trenty, Laurent

    2016-01-01

    Corrosion of steel reinforcement is the main cause of damage for reinforced concrete structures. Iron oxides produced during the corrosion process can induce concrete cracking, loss of adhesion at the steel-concrete interface, loss of reinforcing bar cross-section and even spalling of the concrete cover. In the presented research, the durability problems related to the corrosion of the reinforcement are investigated by combining experimental and numerical studies. However, this paper particul...

  7. Experimental study of the deuteron-induced activation reactions on yttrium

    International Nuclear Information System (INIS)

    Uddin, M.S.; Baba, M.; Hagiwara, M.; Tarkanyi, F.; Ditroi, F.

    2006-01-01

    The aim is accumulation of experimental data and establishment of a consistent database of the Y+d reactions in the frame of systematic investigation of particle-induced nuclear reactions on metals for the production of radioisotopes. The model calculations were performed by TALYS code to make a comparison with the experiment. The thick target integral yields were also deduced from the measured cross-sections for different possible practical applications

  8. Neuropsychological consequences of experimentally-induced anxiety on working memory performance

    OpenAIRE

    Dunger, Warren

    2016-01-01

    Many theories addressing the complex anxiety-cognition interaction are built upon the notion that working memory is vulnerable to the effects of anxiety. However, most research has utilised studies of trait anxiety which does not allow direct inferences to be made between affect and cognitive performance, or exclude confounds such as pre-existing individual differences. As a result, a systematic review was undertaken to explore the neuropsychological consequences of experimentally-induced sta...

  9. Analysis of the heating process in experimental laser-induced thrombosis of microvessels

    Science.gov (United States)

    Petrishchev, Nikolai N.; Mikhailova, Irene

    1996-12-01

    Experimental laser thrombosis is induced in rat mesenteric microvessels. Temperature increase within irradiated microvessels was calculated on the basis of relatively simple heat transfer model and appeared to be near 50 degrees C above the initial value. This temperature increase decay practically to initial level during the period between two subsequent laser impulses. It is stated that the zone of endothelium thermal damage is less than thrombus length along the vessel wall.

  10. A Case of Acute ST-Segment Elevation Myocardial Infarction Mimicking Stress Induced Cardiomyopathy; Demonstration of Typical Echocardiographic Finding Correlated with Unusual Distribution of Left Anterior Descending Coronary Artery.

    Science.gov (United States)

    Shin, Sung Kyun; Jin, Seon-Ah; Park, Yong Kyu; Park, Jae-Hyeong

    2010-09-01

    Stress-induced cardiomyopathy (SCMP) is diagnosed in 1-2% of patients presenting with symptoms suggestive of acute coronary syndrome. Because of sharing many common clinical features with SCMP, acute ST-segment elevation myocardial infarction (STEMI) can be misdiagnosed as SCMP. However, it can be associated with fatal outcome of the patient. Also, diagnosis of SCMP seems to be always challenging to clinicians, especially in the decision of taking coronary angiography which is still invasive and even risky. Here, we present a case with acute STEMI mimicking SCMP as a result of anatomical variation of coronary circulation. In this patient, prompt and early coronary angiography and stent implantation was very helpful.

  11. Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair.

    Science.gov (United States)

    Packard, René R Sevag; Baek, Kyung In; Beebe, Tyler; Jen, Nelson; Ding, Yichen; Shi, Feng; Fei, Peng; Kang, Bong Jin; Chen, Po-Heng; Gau, Jonathan; Chen, Michael; Tang, Jonathan Y; Shih, Yu-Huan; Ding, Yonghe; Li, Debiao; Xu, Xiaolei; Hsiai, Tzung K

    2017-08-17

    This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P < 0.05, n = 7-19). Doxorubicin-injected fish developed ventricular diastolic dysfunction and worsening global cardiac function evidenced by elevated E/A ratios and myocardial performance indexes quantified by pulsed-wave Doppler ultrasound at day 30, followed by normalization at day 60 (P < 0.05, n = 9-20). Treatment with the γ-secretase inhibitor, DAPT, to inhibit cleavage and release of Notch Intracellular Domain (NICD) blocked cardiac architectural regeneration and restoration of ventricular function at day 60 (P < 0.05, n = 6-14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy.

  12. Acute pulmonary injury induced by experimental muscle trauma Lesão pulmonar aguda induzida por trauma muscular experimental

    Directory of Open Access Journals (Sweden)

    Márcia Andréa da Silva Carvalho Sombra

    2011-01-01

    Full Text Available PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6: G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE (2 mg/kg body weight i.p.. Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p. rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung were collected for myeloperoxidase (MPO assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6: G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE (2 mg/kg peso corporal ip. Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97% de 100 ml/kg, i.p. por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão foram coletadas para avaliação da mieloperoxidase (MPO, e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutr

  13. Experimental pathology of local tissue damage induced by Bothrops asper snake venom.

    Science.gov (United States)

    Gutiérrez, José María; Rucavado, Alexandra; Chaves, Fernando; Díaz, Cecilia; Escalante, Teresa

    2009-12-01

    Envenomations by Bothrops asper are often associated with complex and severe local pathological manifestations, including edema, blistering, dermonecrosis, myonecrosis and hemorrhage. The pathogenesis of these alterations has been investigated at the experimental level. These effects are mostly the consequence of the direct action of zinc-dependent metalloproteinases (SVMPs) and myotoxic phospholipases A(2) (PLA(2)s). SVMPs induce hemorrhage, blistering, dermonecrosis and general extracellular matrix degradation, whereas PLA(2)s induce myonecrosis and also affect lymphatic vessels. In addition, the prominent vascular alterations leading to hemorrhage and edema may contribute to ischemia and further tissue necrosis. The mechanisms of action of SVMPs and PLA(2)s are discussed in detail in this review. Venom-induced tissue damage plays also a role in promoting bacterial infection. A prominent inflammatory reaction develops as a consequence of these local pathological alterations, with the synthesis and release of abundant mediators, resulting in edema and pain. However, whether inflammatory cells and mediators contribute to further tissue damage is not clear at present. Muscle tissue regeneration after venom-induced pathological effects is often impaired, thus resulting in permanent tissue loss and dysfunction. SVMP-induced microvessel damage is likely to be responsible of this poor regenerative outcome. Antivenoms are only partially effective in the neutralization of B. asper-induced local effects, and the search for novel toxin inhibitors represents a potential avenue for improving the treatment of this serious aspect of snakebite envenomation.

  14. Experimental investigation of laser-induced bubble dynamics near elastic/soft material in distilled water

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, S; Yamamoto, Y [Graduate Student, Graduate School of Engineering, Chiba University, 1-33 Yayoi, Inage, Chiba, 263-8522 (Japan); Ota, M; Maeno, K, E-mail: maeno@faculty.chiba-u.j [Graduate School of Engineering, Chiba University, 1-33 Yayoi, Inage, Chiba, 263-8522 (Japan)

    2009-02-01

    This study deals with an experimental investigation of the dynamics of laser-induced single bubble near the rigid material plate and near the elastic/soft material plate in the distilled water at room temperature under atmospheric pressure. A pulsed Nd:YAG laser was focused into the distilled water to make plasma and single bubble. The bubble repeated expanding and shrinking motion several times, and then collapsed. This behavior occurred on the sub-millisecond timescale. The solid wall near the bubble makes an asymmetric flow field. Many experiments on the behavior of laser-induced bubble near the rigid material have been reported. The bubble near the solid wall moves toward the rigid wall during its shrinking and rebounding process. The behavior of laser-induced bubble near the soft material, however, has not been well clarified. The soft material such as body tissue can deform and influence the behavior of the laser-induced bubble. Since the high peak power laser has been applied in the field of bioengineering and medical treatment, it is of great importance to clarify the effect of the soft material near the laser-induced cavitation bubble. In this research the behavior of laser-induced bubble near the elastic/soft material was visualized with schlieren method and investigated.

  15. The role of experimentally-induced subacromial pain on shoulder strength and throwing accuracy.

    Science.gov (United States)

    Wassinger, Craig A; Sole, Gisela; Osborne, Hamish

    2012-10-01

    Shoulder injuries often comprise two separate yet related components, structural tissue damage and pain. The role of each of these components on shoulder function is difficult to ascertain. Experimental pain models allow the assessment of consequences of localized pain when applied to healthy individuals. By understanding the role of pain on shoulder function, clinicians will be able to more efficiently assess and treat shoulder injuries. The objective of the study was to evaluate the role of experimentally-induced sub-acromial pain on shoulder isokinetic rotational strength and throwing accuracy. This was a block counterbalanced, crossover, repeated measures study design utilizing 20 individuals without self-reported shoulder or cervical pathology. Shoulder function was measured with and without experimental pain injection (2 mL of 5% hypertonic saline) in the sub-acromial space. Functional tasks consisted of shoulder rotational strength utilizing isokinetic testing and throwing accuracy via the functional throwing performance index. The hypertonic saline induced moderate pain levels in all participants (4.3-5.1/10). Normalized shoulder internal (t = 3.76, p = 0.001) and external (t = 3.12, p = 0.006) rotation strength were both diminished in the painful condition compared to the pain free condition. Throwing accuracy was also reduced while the participants experienced pain (t = 3.99, p = 0.001). Moderate levels of experimental shoulder pain were sufficient to negatively influence shoulder strength and throwing accuracy in participants without shoulder pathology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Spectroscopic evaluation of painted layer structural changes induced by gamma radiation in experimental models

    International Nuclear Information System (INIS)

    Manea, Mihaela M.; Moise, Ioan V.; Virgolici, Marian; Negut, Constantin D.; Barbu, Olimpia-Hinamatsuri; Cutrubinis, Mihalis; Fugaru, Viorel; Stanculescu, Ioana R.; Ponta, Corneliu C.

    2012-01-01

    The degradation of cultural heritage objects by insects and microorganisms is an important issue for conservators, art specialists and humankind in general. Gamma irradiation is an efficient method of polychrome wooden artifacts disinfestation. Color changes and other modifications in the physical chemical properties of materials induced by gamma irradiation are feared by cultural heritage responsible committees and they have to be evaluated objectively and precisely. In this paper FTIR and FT-Raman spectroscopy methods were used to investigate the structural changes in some experimental models of tempera paint layers on wood following 11 kGy gamma irradiation at two dose rates. Radiation chemistry depends on the particular pigment, matrix formed by protein, resin (in case of varnished samples) and water presence. For the majority of painted layer in experimental models very small spectral variations were observed. Small changes in the FTIR spectra were observed for the raw sienna experimental model: for the higher dose rate the egg yolk protein oxidation peaks and the CH stretching bands due to lipids degradation products increased. - Highlights: ► Experimental models of tempera paint layers on wood were γ-irradiated at two dose rates. ► Changes induced by γ-irradiation were evaluated by vibrational spectroscopy. ► Minor spectral variations of painted layer were observed. ► Raw sienna FTIR spectra showed little changes of egg yolk and lipids at higher dose rate. ► Gamma irradiation is recommended for disinfection of painted wooden artifacts.

  17. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    Science.gov (United States)

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright 2004 John Wiley & Sons, Ltd.

  18. LncRNA TUG1 serves an important role in hypoxia-induced myocardial cell injury by regulating the miR‑145‑5p‑Binp3 axis.

    Science.gov (United States)

    Wu, Zhongwei; Zhao, Shengji; Li, Chunfu; Liu, Chaoquan

    2018-02-01

    The aim of the present study was to investigate the function of long non‑coding RNA TUG1 in hypoxia‑induced myocardial cell injury and to explore the potential molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic and normoxic conditions. TUG1 expression under hypoxic conditions was then detected. The effects of TUG1 overexpression on viability, apoptosis, migration and invasion were assayed. In addition, the microRNA (miR)‑145‑5p expression was detected. Following H9c2 cell transfection with miR‑145‑5p mimics, the H9c2 cell viability, apoptosis, migration and invasion were also detected. Additionally, the target gene of miR‑145‑5p was assayed by Luciferase reporter assay. The protein expressions of Wnt‑3a, Wnt5a, and β‑catenin in H9c2 cells under hypoxic conditions were also determined. The results revealed that hypoxia induced injury in H9c2 cells, including inhibiting cell viability, migration and invasion, and promoting cell apoptosis. Overexpression of TUG1 aggravated hypoxia‑induced injury in H9c2 cells. In addition, miR‑145‑5p was negatively regulated by TUG1, and TUG1 overexpression aggravated hypoxia‑induced injury via the downregulation of miR‑145‑5p. Furthermore, B‑cell lymphoma 2 interacting protein 3 (Bnip3) was a target of miR‑145‑5p, and overexpression of Bnip3 aggravated hypoxia‑induced cell injury by activating Wnt/β‑catenin signaling pathways in H9c2 cells. In conclusion, overexpression of TUG1 aggravated hypoxia‑induced injury in cardiomyocytes by regulating the miR‑145‑5p‑Binp3 axis. Activation of the Wnt/β‑catenin signaling pathway may be a key mechanism to mediate the role of TUG1 in regulating hypoxia‑induced myocardial injury. TUG1 may be an effective diagnostic marker and therapeutic target for myocardial ischemia.

  19. LncRNA TUG1 serves an important role in hypoxia-induced myocardial cell injury by regulating the miR-145-5p-Binp3 axis

    Science.gov (United States)

    Wu, Zhongwei; Zhao, Shengji; Li, Chunfu; Liu, Chaoquan

    2018-01-01

    The aim of the present study was to investigate the function of long non-coding RNA TUG1 in hypoxia-induced myocardial cell injury and to explore the potential molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic and normoxic conditions. TUG1 expression under hypoxic conditions was then detected. The effects of TUG1 overexpression on viability, apoptosis, migration and invasion were assayed. In addition, the microRNA (miR)-145-5p expression was detected. Following H9c2 cell transfection with miR-145-5p mimics, the H9c2 cell viability, apoptosis, migration and invasion were also detected. Additionally, the target gene of miR-145-5p was assayed by Luciferase reporter assay. The protein expressions of Wnt-3a, Wnt5a, and β-catenin in H9c2 cells under hypoxic conditions were also determined. The results revealed that hypoxia induced injury in H9c2 cells, including inhibiting cell viability, migration and invasion, and promoting cell apoptosis. Overexpression of TUG1 aggravated hypoxia-induced injury in H9c2 cells. In addition, miR-145-5p was negatively regulated by TUG1, and TUG1 overexpression aggravated hypoxia-induced injury via the downregulation of miR-145-5p. Furthermore, B-cell lymphoma 2 interacting protein 3 (Bnip3) was a target of miR-145-5p, and overexpression of Bnip3 aggravated hypoxia-induced cell injury by activating Wnt/β-catenin signaling pathways in H9c2 cells. In conclusion, overexpression of TUG1 aggravated hypoxia-induced injury in cardiomyocytes by regulating the miR-145-5p-Binp3 axis. Activation of the Wnt/β-catenin signaling pathway may be a key mechanism to mediate the role of TUG1 in regulating hypoxia-induced myocardial injury. TUG1 may be an effective diagnostic marker and therapeutic target for myocardial ischemia. PMID:29207102

  20. Exercise-induced changes in left ventricular filling pressure after myocardial infarction assessed with simultaneous right heart catheterization and Doppler echocardiography

    DEFF Research Database (Denmark)

    Andersen, Mads J; Ersbøll, Mads; Gustafsson, Finn

    2013-01-01

    To assess whether changes in E/e´ (the ratio between peak early mitral inflow velocity (E) and peak early mitral annulus velocity (e´)) during exercise reflect changes in filling pressure in patients with a recent myocardial infarction (MI) and mild to moderate diastolic dysfunction at rest. A low...

  1. Effects of the calcium channel antagonist mibefradil on haemodynamic and morphological parameters in myocardial infarction-induced cardiac failure in rats

    NARCIS (Netherlands)

    Sandmann, S.; Spitznagel, H.; Chung, O.; Xia, Q. G.; Illner, S.; Jänichen, G.; Rossius, B.; Daemen, M. J.; Unger, T.

    1998-01-01

    Calcium channel antagonists (CCA) have been proposed for the prevention of cardiac events after myocardial infarction (MI). Mibefradil is a CCA featuring a selective blockade of T-type Ca2(+)-channels. The aim of the study was to characterize the effects of mibefradil on haemodynamic and

  2. [Protective effect of Helianthus annuus (sunflower) on myocardial infarction in New Zealand rabbit].

    Science.gov (United States)

    Guardia-Espinoza, Edith; Herrera-Hurtado, Gianina Liseth del Carmen; Garrido-Jacobi, Saúl; Cárdenas-Peralta, Danitza; Martínez-Romero, Christian; Hernández-Figueroa, Pedro; Condori-Calizaya, Mary; La Barrera-Llacchua, Juan; Flores-Ángeles, Miguel

    2015-01-01

    Determine the protective effect of oil Helianthus annuus (Sunflower) on myocardial infarction induced by epinephrine in New Zealand rabbits. The rabbits were randomized into five groups (8 per group): blank, negative control, experimental 1 (10 mg / kg), experimental 2 (20 mg / kg) and three experimental (40 mg/ kg). Experimental groups 1, 2 and 3 received Helianthus annuus oil for two weeks. Epinephrine (2 mg/Kg) to the negative, Experimental Control 1, 2 and 3 groups was given over two consecutive days with an interval of 24 h after pretreatment with oil. Twenty four hours after the last administration, the rabbits were anesthetized and sacrificed. Serum troponin I and polymorphonuclear evaluated by .mu.m.sup.2. Significant difference between the negative control group and the experimental groups 1, 2 and 3 was found in the serum variables troponin I and polymorphonuclear by .mu.m.sup.2. Helianthus annuus oil at doses of 20 mg/kg has protective effect on myocardial infarction induced by epinephrine in New Zealand rabbits.

  3. Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats

    Directory of Open Access Journals (Sweden)

    Eduardo C. A. Veiga

    2011-01-01

    Full Text Available OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean + SEM were analyzed using a two-way ANOVA model followed byTukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 + 3.04 vs. 37.59 + 3.07. In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 + 1.52 vs. 45.48 + 3.49. The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 + 2% and 39 + 3%, respectively were smaller than those for the exercise sham surgery (ES, 67+1% and sedentary sham surgery (SS, 69 + 2% groups. The E/A was higher in the sedentary myocardial infarction (4.4 + 0.3 and exercised myocardial infarction (5.5 + 0.3 rats than in the SS (2.4 + 0.1 and ES (2.2 + 0.1 rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.

  4. Effect of eating on thallium myocardial imaging

    International Nuclear Information System (INIS)

    Wilson, R.A.; Sullivan, P.J.; Okada, R.D.; Boucher, C.A.; Morris, C.; Pohost, G.M.; Strauss, H.W.

    1986-01-01

    To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The 201 Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of 201 Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed 201 Tl images causes increased 201 Tl myocardial clearance rates and may alter 201 Tl myocardial redistribution over time

  5. Experimental diabetes induces structural, inflammatory and vascular changes of Achilles tendons.

    Directory of Open Access Journals (Sweden)

    Rodrigo R de Oliveira

    Full Text Available This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS and nitrate and nitrite level. The Achilles tendon thickness (µm/100g of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98 vessels/field when compared to the control group 0.89 (1.68 vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18 vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99 vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.

  6. Electron microscopic study of spontaneous and experimentally induced leukemia in IRC mice

    International Nuclear Information System (INIS)

    Hiraki, S.; Ranadive, K.J.; Dmochowski, L.

    1974-01-01

    Spontaneous, serially transplanted, and experimentally induced leukemias of ICRC mice were studied by electron microscopy in an attempt to detect the presence of virus particles, if any, and to observe the influence of chemical and hormonal treatment on the presence of these virus particles. The first series of experiments included spontaneous, serially transplanted, and radiation-induced leukemia. The paucity of type C virus particles was quite conspicuous in spontaneous leukemia. Serially transplanted and radiation-accelerated leukemic lesions showed the presence of some type C and intracisternal type A particles. Found in two of these leukemic lesions (thymus and lymphosarcoma), in addition to type C virus particles, were budding and some mature type B virus particles, and numerous intracytoplasmic type A particles. ''Viropexis'' of type B virus particles has been observed in the lymphosarcoma and in a leukemic thymus gland. The second series of experiments included leukemia induced in ovariectomized ICRC mice with 20-methylcholanthrene (MCA), pituitary transplants, and ovarian hormones (estradiol and estradiol-progesterone). In ovariectomized ICRC mice, leukemic lesions induced by MCA or pituitary transplants, or by MCA and pituitary transplants, showed type C virus particles and, in most cases, intracisternal type A particles. In leukemia induced in ovariectomized ICRC mice by MCA and estradiol, numerous intracytoplasmic type A particles were observed but no type C virus particles

  7. Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.

    OpenAIRE

    Billman, G E; Hallaq, H; Leaf, A

    1994-01-01

    A specially prepared dog model of myocardial infarction was used to test the efficacy of the long-chain polyunsaturated fish oil omega 3 fatty acids eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) acids to prevent ischemia-induced malignant cardiac arrhythmias. The dogs had sustained a prior experimental myocardial infarction from ligation of the left anterior descending coronary artery, and a hydraulic cuff was implanted around the left circumflex artery at that operation. After r...

  8. Effect of Kaempferol Pretreatment on Myocardial Injury in Rats.

    Science.gov (United States)

    Vishwakarma, Anamika; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Kandasamy, Arunvikram; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Kumar, Ajay; Kumar, Asok; Kumar, Dinesh

    2018-01-20

    The present study was undertaken to evaluate the effect of kaempferol in isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered subcutaneously for two subsequent days to induce myocardial injury. Assessment of myocardial injury was done by estimation of hemodynamic functions, myocardial infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro-inflammatory cytokines and histopathology of heart and liver. Rats pretreated with kaempferol showed reduction in the myocardial infarcted area and heart rate. However, no improvement was observed in change in body weight, mean arterial, systolic and diastolic blood pressure. Kaempferol showed significant decrease in serum LDH, CK-MB, troponin-I and lipid profile. However, highest dose of kaempferol did not reduce the serum triglyceride level. Further, antioxidant enzymes, SOD and catalase, were also higher. However, reduced glutathione, serum SGOT and creatinine did not show any improvement. Kaempferol showed reduction in MDA level. Kaempferol at highest dose showed reduction in pro-MMP-2 expression and MMP-9 level. mRNA expression level of TNF-α was not different in kaempferol-pretreated myocardial injured rats with ISP-alone group. Pretreatment with kaempferol at highest dose showed mild mononuclear infiltration and degenerative changes in heart tissue section of myocardial injured rats. Rats pretreated with kaempferol at higher concentration showed normal cordlike arrangement of hepatocytes with moderate swelling of hepatocytes (vacuolar degeneration) around the central vein. Study suggests that kaempferol attenuated lipid profile, infarcted area and oxidative stress in ISP-induced myocardial injury in rats.

  9. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

    Science.gov (United States)

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

    2014-06-01

    Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  10. Ramipril inhibits AGE-RAGE-induced matrix metalloproteinase-2 activation in experimental diabetic nephropathy.

    Science.gov (United States)

    Fukami, Kei; Yamagishi, Sho-Ichi; Coughlan, Melinda T; Harcourt, Brooke E; Kantharidis, Phillip; Thallas-Bonke, Vicki; Okuda, Seiya; Cooper, Mark E; Forbes, Josephine M

    2014-01-01

    Advanced glycation end products (AGE)-receptor for AGE (RAGE) axis and renin-angiotensin system (RAS) play a role in diabetic nephropathy (DN). Matrix metalloproteinase-2 (MMP-2) activation also contributes to DN. However, the pathological interaction among AGE-RAGE, RAS and MMP-2 in DN remains unknown. We examined here the involvement of AGE and RAS in MMP-2 activation in streptozotocin (STZ)-induced diabetic rats and in AGE-exposed rat renal proximal tubular cells (RPTCs). Experimental diabetes was induced in 6-week-old male Sprague-Dawley (SD) rats by intravenous injection of STZ. Diabetic rats received ramipril (3 mg/kg body weight/day) or vehicle for 32 weeks. AGE-modified rat serum albumin (AGE-RSA) or RSA was intraperitoneally administrated to 6-week-old male SD rats for 16 weeks. RPTCs were stimulated with 100 μg/ml AGE-modified bovine serum albumin (AGE-BSA) or BSA in the presence or absence of 10(-7) M ramiprilat, an inhibitor of angiotensin-converting enzyme or 100 nM BAY11-7082, an IκB-α phosphorylation inhibitor. AGE and RAGE expression levels and MMP-2 activity in the tubules of diabetic rats was significantly increased in association with increased albuminuria, all of which were blocked by ramipril. AGE infusion induced tubular MMP-2 activation and RAGE gene expression in SD rats. Ramiprilat or BAY11-7082 inhibited the AGE-induced MMP-2 activation or reactive oxygen species generation in RPTCs. Angiotensin II increased MMP-2 gene expression in RPTCs, which was blocked by BAY11-7082. Our present study suggests the involvement of AGE-RAGE-induced, RAS-mediated MMP-2 activation in experimental DN. Blockade of AGE-RAGE axis by ramipril may protect against DN partly via suppression of MMP-2.

  11. Cardiac MRI for myocardial ischemia.

    LENUS (Irish Health Repository)

    Daly, Caroline

    2013-01-01

    Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging.

  12. Experimental ‏review ‏of ‏cobalt ‏induced cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Igor ‏V. Zadnipryany

    2017-03-01

    The primary morphological alteration is mitochondrial damage that possibly reflects an enzymatic block of oxidative decarboxylation at pyruvate and ketogluterate levels. Due to that myofibrils of the myocardial cells were affected highlighting that the main cause of myofibril reduction could be a lower oxygen intake in the perinuclear area. The reduction of the contractile support of myocardial cells can explain the possible myocardial dysfunction. Nuclear changes were consistent with sarcoplasmic alterations, our study showing deformed, twisted, hyperchromatic nuclei with heterogeneous chromatin and even disintegrating nuclei. Changes of the interstitial connective tissue were sometimes extensive and sometimes barely noticeable. The most common alteration of this structure was the onset and development of a mainly perivascular collagen fibrillogenetic process.

  13. The effect of experimentally induced sedentariness on mood and psychobiological responses to mental stress.

    Science.gov (United States)

    Endrighi, Romano; Steptoe, Andrew; Hamer, Mark

    2016-03-01

    Evidence suggests a link between sedentary behaviours and depressive symptoms. Mechanisms underlying this relationship are not understood, but inflammatory processes may be involved. Autonomic and inflammatory responses to stress may be heightened in sedentary individuals contributing to risk, but no study has experimentally investigated this. To examine the effect of sedentary time on mood and stress responses using an experimental design. Forty-three individuals were assigned to a free-living sedentary condition and to a control condition (usual activity) in a cross-over, randomised fashion and were tested in a psychophysiology laboratory after spending 2 weeks in each condition. Participants completed mood questionnaires (General Health Questionnaire and Profile of Mood States) and wore a motion sensor for 4 weeks. Sedentary time increased by an average of 32 min/day (P = 0.01) during the experimental condition compared with control. Being sedentary resulted in increases in negative mood independent of changes in moderate to vigorous physical activity (ΔGHQ = 6.23, ΔPOMS = 2.80). Mood disturbances were associated with greater stress-induced inflammatory interleukin-6 (IL-6) responses (β = 0.37). Two weeks of exposure to greater free-living sedentary time resulted in mood disturbances independent of reduction in physical activity. Stress-induced IL-6 responses were associated with changes in mood. © The Royal College of Psychiatrists 2016.

  14. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

    Directory of Open Access Journals (Sweden)

    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experiment