TY  - THES
A1  - Hofmann, Ulrich Dietmar Walter
T1  - Einfluss von Tumor Nekrose Faktor-Alpha (TNF- Alpha) auf die myokardiale Energetik
T1  - TNF-Alpha impairs economy of contraction in rat myocardium
N2  - Es konnte erstmals gezeigt werden, dass Tumor Nekrose Faktor-α (TNF- α) (TNF-α) in pathophysiologisch relevanten Konzentrationen neben seiner bekannten negativ inotropen Wirkung einen deutlichen Effekt auf die myokardiale Energetik im Myokard der Ratte besitzt. Dieser wurde anhand des Sauerstoffverbrauchs an rechtsventrikulären Muskelstreifenpräparaten quantifiziert. Der erhöhte Energieumsatz bei gleichzeitig reduzierter myokardialer Arbeit, d.h. der gesteigerte spezifische Sauerstoffverbrauch, basiert auf einer verschlechterten Ökonomie des Kontraktionsprozesses. Diese schnelle Wirkung auf die myokardiale Energetik ist durch einen Sphingolipid Signaltransduktionsweg vermittelt. Dagegen spielt wohl für den mechanischen Effekt von TNF-α sowohl NO, als auch Sphingosin eine Rolle.
N2  - Objective: Several experimental studies have demonstrated that tumor necrosis factor-α (TNF-α) impairs myocardial contractility. It was the aim of the present study to test the hypothesis that TNF-α influences myocardial energy metabolism as well. Methods: Oxygen consumption (MVO2) of isometrically contracting trabeculae isolated from right ventricular rat myocardium was analyzed using a clark-type oxygen probe. The slope of the force-time integral-MVO2 regression line indicates economy of contraction. Results: TNF-α impaired myocardial economy without altering baseline MVO2. Incubation with TNF-α in the presence of the NO-synthase inhibitor L-NAME further impaired myocardial economy. Pre-incubation with the ceramidase inhibitor NOE abrogated the TNF-α effect on myocardial economy. The negative inotropic effect of TNF-α was observed in NOE, but not in L-NAME pre-incubated muscle fibers. Moreover, exogenous sphingosine mimicked the TNF-α effect on mechanics and energetics. Conclusion: TNF-α impairs the economy of chemo-mechanical energy transduction primarily through a sphingosine-mediated pathway.
KW  - Myokardiale Energetik
KW  - Tumor Nekrose Faktor-Alpha
KW  - Zytokine
KW  - Sauerstoffverbrauch
KW  - myocardial energetics
KW  - tumor necrosis factor-Alpha
KW  - cytokines
KW  - oxygen consumption
Y1  - 2006
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-23663
ER  - 
TY  - JOUR
A1  - Hofmann, Ulrich
A1  - Frantz, Stefan
T1  - How can we cure a heart "in flame"? A translational view on inflammation in heart failure
JF  - Basic Research in Cardiology
N2  - The prevalence of chronic heart failure is still increasing making it a major health issue in the 21st century. Tremendous evidence has emerged over the past decades that heart failure is associated with a wide array of mechanisms subsumed under the term "inflammation". Based on the great success of immuno-suppressive treatments in auto-immunity and transplantation, clinical trials were launched targeting inflammatory mediators in patients with chronic heart failure. However, they widely lacked positive outcomes. The failure of the initial study program directed against tumor necrosis factor-a led to the search for alternative therapeutic targets involving a broader spectrum of mechanisms besides cytokines. We here provide an overview of the current knowledge on immune activation in chronic heart failure of different etiologies, summarize clinical studies in the field, address unresolved key questions, and highlight some promising novel therapeutic targets for clinical trials from a translational basic science and clinical perspective.
KW  - cytokines
KW  - immuno-modulation
KW  - heart failure
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134497
VL  - 108
IS  - 356
ER  -