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  1. Book ; Online ; Thesis: Untersuchungen von Phospho-AMPK a, VEGF-A und VEGF-R2 im Myokard sowie Analysen von morphologischen Veränderungen im Modell der chronischen Herzinsuffizienz induziert durch sequentielle, repetitive koronare Mikroembolisation an der Spezies Schaf

    Heidrich, Florian

    2010  

    Abstract: Die Basis und zugleich Mittelpunkt dieser Dissertation bildete das Modell der chronischen Herzinsuffizienz (vergleichbar NYHA III), induziert durch sequentielle, repetitive koronare Mikroembolisation an der Spezies Schaf. Im Rahmen dieser Dissertation ... ...

    Author's details vorgelegt von Florian Heidrich
    Abstract Die Basis und zugleich Mittelpunkt dieser Dissertation bildete das Modell der chronischen Herzinsuffizienz (vergleichbar NYHA III), induziert durch sequentielle, repetitive koronare Mikroembolisation an der Spezies Schaf. Im Rahmen dieser Dissertation gelang erstmalig eine morphologische Systemvalidierung (HE- und PSR-Färbungen von Myokard-, Leber- und Nierengewebe) zur Prüfung eines Vorwärts- sowie Rückwärtsversagens, welches bereits durch hämodynamische Analysen verifiziert wurde. Des Weiteren wurde mit Hilfe der RT-PCR und des Western Blotting Phospho-AMPK a, VEGF-A und VEGF-R2 analysiert. Ziel war die Definition von Kompensationsmechanismen, die für eine Adaptation an die induzierte Druck- und Volumenbelastung verantwortlich sein könnten. AMPK agiert als zentrales Schlüsselenzym im kardialen Energiestoffwechsel und besitzt verschiedene kardioprotektive Eigenschaften. Mit VEGF-A und VEGF-R2 wurden obligate Parameter der Neoangiogenese (suffiziente Kollateralisierung) untersucht. Repetitive, sequentielle Mikroembolisation induziert eine ischämische Kardiomyopathie und führen konsekutiv zu pathologischen Veränderungen der Leber und Niere. Quantitative sowie qualitative Analysen zeigten einen signifikanten Anstieg der Phosphorylierung von AMPK. Die ermittelten Werte von VEGF-A und VEGF-R2 lagen stets im Bereich der Kontrollgruppe. Somit könnte lediglich Phospho-AMPK a als möglicher Kompensationsmechanismus postuliert werden. Die retrospektive Betrachtung aller Ergebnisse ergab eine führende rechtsventrikuläre Schädigung. Infolgedessen konnte eindrucksvoll herausgearbeitet werden, dass sich das etablierte Versuchstiermodell primär für Studien einer Globalinsuffizienz und nicht hingegen, wie angenommen, für Studien einer isolierten Linksherzinsuffizienz eignet.
    Language German
    Size Online-Ressource (PDF-Datei: 111 S., 10.000 KB), Ill., graph. Darst
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Göttingen, 2011
    Database Former special subject collection: coastal and deep sea fishing

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  2. Conference proceedings: Partizipation im Forschungspraxennetz RESPoNsE: Praxisbeiräte – ein Werkstattbericht

    Wolf, Florian / Akdenizli, Kemal / Bleidorn, Jutta / Fleischhauer, Christian / Fritsch, Sarah / Heidrich, Florian / Heintze, Christoph / Henße, Jana / Holz, Stefanie / Isbrecht, Ina / Kaden, Frank / Kümpel, Lisa / Kuschick, Doreen / Lieb, Christian / Medrow, Natascha / Mühlberg, Juliane / Neidhardt-Akdenizli, Andrea / Reicherdt, Isabelle / Riese, Kerstin /
    Rost, Liljana / Steenweg, Lydia / Stengler, Katja / Toutaoui, Kahina / Zitterbart, Ulf / Döpfmer, Susanne

    2021  , Page(s) V–06–01

    Event/congress 55. Kongress für Allgemeinmedizin und Familienmedizin; Lübeck; Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin; 2021
    Keywords Medizin, Gesundheit
    Publishing date 2021-09-17
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/21degam029
    Database German Medical Science

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  3. Book ; Online ; Thesis: Untersuchungen von Phospho-AMPK α, VEGF-A und VEGF-R2 im Myokard sowie Analysen von morphologischen Veränderungen im Modell der chronischen Herzinsuffizienz induziert durch sequentielle, repetitive koronare Mikroembolisation an der Spezies Schaf

    Heidrich, Florian [Verfasser] / Schmitto, Jam [Akademischer Betreuer] / Schöndube, Friedrich [Akademischer Betreuer] / Maier, Lars [Akademischer Betreuer]

    2011  

    Author's details Florian Heidrich. Gutachter: Friedrich Schöndube ; Lars Maier. Betreuer: Jam Schmitto
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Niedersächsische Staats- und Universitätsbibliothek Göttingen
    Publishing place Göttingen
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  4. Article ; Online: AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart.

    Heidrich, Florian / Schotola, Hanna / Popov, Aron F / Sohns, Christian / Schuenemann, Julia / Friedrich, Martin / Coskun, Kasim O / von Lewinski, Dirk / Hinz, Jose / Bauer, Martin / Mokashi, Suyog A / Sossalla, Samuel / Schmitto, Jan D

    Current cardiology reviews

    2011  Volume 6, Issue 4, Page(s) 337–342

    Abstract: Adenosine monophosphate - activated kinase (AMPK) plays a key role in the coordination of the heart's anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated ... ...

    Abstract Adenosine monophosphate - activated kinase (AMPK) plays a key role in the coordination of the heart's anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α - subunit (63kDa), a regulating β - subunit (38kDa) and a γ - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ - subunit is the step which activates AMPK. AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential. In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.
    Language English
    Publishing date 2011-10-31
    Publishing country United Arab Emirates
    Document type Journal Article
    ISSN 1875-6557
    ISSN (online) 1875-6557
    DOI 10.2174/157340310793566073
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hemodynamic changes in a model of chronic heart failure induced by multiple sequential coronary microembolization in sheep.

    Schmitto, Jan Dieter / Coskun, Kasim Oguz / Coskun, Sinan Tolga / Ortmann, Philipp / Vorkamp, Tobias / Heidrich, Florian / Sossalla, Samuel / Popov, Aron-Frederik / Tirilomis, Theodor / Hinz, José / Heuer, Jan / Quintel, Michael / Chen, Frederick Yen-Ching / Schöndube, Friedrich Albert

    Artificial organs

    2009  Volume 33, Issue 11, Page(s) 947–952

    Abstract: Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model ...

    Abstract Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 +/- 2 kg), chronic heart failure was induced under fluoroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 microm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3-week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan-Ganz catheter (mean pulmonary arterial pressure [PAP mean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre- and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 +/- 4 bpm [base] to 93 +/- 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 +/- 5 [base] to 38 +/- 7 [3 mo][P < 0.05]), and increased body weight 77 +/- 2 kg to 81 +/- 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.
    MeSH term(s) Animals ; Disease Models, Animal ; Electrocardiography ; Embolism/surgery ; Female ; Heart/physiopathology ; Heart Failure/physiopathology ; Heart Failure/surgery ; Hemodynamics ; Microspheres ; Myocardium/pathology ; Sheep
    Language English
    Publishing date 2009-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 441812-8
    ISSN 1525-1594 ; 0160-564X
    ISSN (online) 1525-1594
    ISSN 0160-564X
    DOI 10.1111/j.1525-1594.2009.00921.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The role of phospho-adenosine monophosphate-activated protein kinase and vascular endothelial growth factor in a model of chronic heart failure.

    Heidrich, Florian / Sossalla, Samuel / Schotola, Hanna / Vorkamp, Tobias / Ortmann, Philipp / Popov, Aron F / Coskun, Kasim O / Rajab, Taufiek K / Friedrich, Martin / Sohns, Christian / Hinz, Jose / Bauer, Martin / Quintel, Michael / Schöndube, Friedrich A / Schmitto, Jan D

    Artificial organs

    2010  Volume 34, Issue 11, Page(s) 969–979

    Abstract: We established a stable and reproducible animal model of chronic heart failure (CHF) in sheep to investigate biomolecular changes. Therefore, two biomarkers, adenosine monophosphate-activated protein kinase (AMPK) and vascular endothelial growth factor-A ...

    Abstract We established a stable and reproducible animal model of chronic heart failure (CHF) in sheep to investigate biomolecular changes. Therefore, two biomarkers, adenosine monophosphate-activated protein kinase (AMPK) and vascular endothelial growth factor-A (VEGF-A) were examined to reveal their role during chronic ischemic conditions of the heart. AMPK was studied because it plays an important role in cellular energy homeostasis and its upregulation is associated with myocardial ischemia, whereas VEGF-A was studied because it acts as an important signaling protein for neoangiogenesis. We examined 15 juvenile sheep (mean weight, 78±4kg; control, n=3; ShamOP, n=2; coronary microembolization [CME], n=10). CHF was induced under fluoroscopic guidance by multiple sequential microembolizations (MEs) through bolus injection of polysterol microspheres (90µm, n=25.000) into the left main coronary artery. CME was repeated up to three times at 2- to 3-week intervals until animals started to develop stable signs of CHF. All animals were followed for 3 months. Phosphorylation of AMPK, marking the activated protein form, was detected by Western blotting. VEGF-A and vascular endothelial growth factor-receptor 2 (VEGF-R2) mRNA were detected by real-time polymerase chain reaction. Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was used as a reference housekeeping gene. All 10 CHF animals developed clinical signs of CHF as indicated by a significant decrease of cardiac output, decreased ejection fraction, as well as occurrence of tachycardia and tachypnoea. Western blots showed significant phosphorylation of AMPK in CME animals compared to the control group (phospho-adenosine monophosphate-activated protein kinase α) (GAPDH control: 0.0, CME left ventricle [LV]: 0.39±0.20, CME right ventricle [RV]: 0.53±0.30; P<0.05). VEGF-A and VEGF-R2 expression in CME animal myocardium was within the range of the control group, but this data did not reach statistical significance due to the small size of this group. While microinjection was performed into the left main coronary artery, phosphorylation of AMPK and expression of VEGF-A and VEGF-R2 were significantly higher in the RV than in the LV. Multiple sequential intracoronary MEs can effectively induce myocardial dysfunction with clinical and biomolecular signs of chronic ischemic cardiomyopathy. Quantitative analysis of biomolecular markers showed a significantly higher phosphorylation of AMPK in CHF animals compared with control myocardium.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Animals ; Biomarkers/metabolism ; Blotting, Western ; Chronic Disease ; Disease Models, Animal ; Enzyme Activation ; Female ; Heart Failure/enzymology ; Heart Failure/etiology ; Heart Failure/physiopathology ; Heart Ventricles/enzymology ; Injections, Intra-Arterial ; Microspheres ; Myocardium/enzymology ; Phosphorylation ; Polystyrenes/administration & dosage ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sheep ; Time Factors ; Up-Regulation ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/genetics ; Vascular Endothelial Growth Factor Receptor-2/metabolism
    Chemical Substances Biomarkers ; Polystyrenes ; RNA, Messenger ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2010-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 441812-8
    ISSN 1525-1594 ; 0160-564X
    ISSN (online) 1525-1594
    ISSN 0160-564X
    DOI 10.1111/j.1525-1594.2010.01121.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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