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  • 1
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Hämorrhagischer Schock ; Leukozytenadhäsion ; Lebermikrozirkulation ; Intravitalmikroskopie ; Key words Haemorrhagic shock ; Leukocyte adhesion ; Hepatic microcirculation ; Intravital microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen- derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamin-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model. Methods: Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP=40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer’s (RILA, n=10), gelatine (GELA, n=10), hydroxyethyl starch (HES, n=10), or deferoxamine-conjugated HES (DFO, n=8) solution (MAP≥70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microsscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation. Results: Resuscitation resulted in restoration of MAP to ≥70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO. Conclusion: DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.
    Notes: Zusammenfassung Fragestellung: Die Synthese der während der Reperfusion ischämischen Gewebes aus der Haber-Weiss-Reaktion Fe-abhängig hervorgehenden toxischen Sauerstoffradikale kann durch Deferoxamin, einen potenten Fe-Chelator, verringert werden. Die vorliegende Studie untersucht eine Deferoxamin-konjugierte Hydroxyethylstärkelösung auf ihre antioxidativen Eigenschaften und Auswirkungen auf die hepatische Mikrozirkulation am hämorrhagischen Schockmodell der Ratte. Methodik: Sprague-Dawley-Ratten wurden in Pentobarbitalanästhesie tracheotomiert, für ein invasives hämodynamisches Monitoring präpariert und einem hämorrhagischen Schock unterzogen (MAP=40 mm Hg während 60 min). Die blutfreie Volumentherapie wurde entweder mit Ringerlaktat (RILA; n=10), Gelatinelösung (GELA; n=10), Hydroxyethylstärke (HES; n=10) oder mit Deferoxamin-konjugierter Hydroxyethylstärkelösung (DFO; n=8) durchgeführt (MAP≥70 mm Hg). Eine Studie nach Beginn der Volumentherapie wurde die Mikrozirkulation der Leber intravitalmikroskopisch untersucht und die Glutathionkonzentration im Leberhomogenat sowie die Thiobarbitursäure-reaktiven Substanzen als Marker der Lipidperoxidation gemessen. Ergebnisse: Mit jeder der verwendeten Volumenersatzlösungen konnte der MAP innerhalb kurzer Zeit auf ≥70 mm Hg angehoben werden. In der mit DFO behandelten Gruppe konnte eine signifikant geringere Abnahme an reduziertem Glutathion im Lebergewebe sowie eine geringere Zunahme der Lipidperoxidation als Zeichen des verminderten oxidativen Stresses beobachtet werden. Die schockinduzierte verstärkte Leukozytenadhäsion in Lebersinusoiden wurde durch DFO signifikant vermindert. Schlußfolgerung: DFO vermindert signifikant den schockinduzierten oxidativen Streß, schwächt damit die frühe Entzündungsreaktion ab und bewirkt eine Verbesserung der Lebermikrozirkulation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 74 (1996), S. 51-58 
    ISSN: 1432-1440
    Keywords: Key words Tumor necrosis factor ; Hemorrhagic shock ; Leukocyte adhesion ; Intravital microscopy ; Liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The relevance of tumor necrosis factor-α (TNF-α) inducing early inflammatory reactions in the liver after hemorrhagic shock, for example, leukocyte adhesion, has been well described. This study evaluated the anti-inflammatory effects of a monoclonal antibody against TNF-α (TN3.19.12) in terms of the time of application, namely, prior to shock induction, at the time of resuscitation, and after resuscitation. The hepatic microcirculation was investigated by intravital fluorescence microscopy in female Sprague-Dawley rats undergoing severe hemorrhagic shock for 60 min and subsequent resuscitation. TN3.19.12 or placebo was given in a randomized and blinded manner either 60 min prior to shock induction, 1 min prior to resuscitation, or 15 min after the onset of resuscitation. The number of firmly adherent leukocytes in the livers of treated animals depended on the time of application of TN3.19.12. Leukocyte adhesion was significantly reduced when TN3.19.12 was given prior to shock induction or at the time of resuscitation and was less effective when administered after the onset of resuscitation. The results further confirm that TNF-α initiates very early pathological leukocyte adhesion in the liver 5 h following shock. Inhibition of leukocyte adhesion after shock, however, depends strongly on the time of TNF-α blocking. While TN3.19.12 prior to shock induction resulted in most effective attenuation, only very early treatment allowed limitation of posttraumatically increased leukocyte adhesion.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 74 (1996), S. 51-58 
    ISSN: 1432-1440
    Keywords: Tumor necrosis factor ; Hemorrhagic shock ; Leukocyte adhesion ; Intravital microscopy ; Liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relevance of tumor necrosis factor-α (TNF-α) inducing early inflammatory reactions in the liver after hemorrhagic shock, for example, leukocyte adhesion, has been well described. This study evaluated the anti-inflammatory effects of a monoclonal antibody against TNF-α (TN3.19.12) in terms of the time of application, namely, prior to shock induction, at the time of resuscitation, and after resuscitation. The hepatic micro-circulation was investigated by intravital fluorescence microscopy in female Sprague-Dawley rats undergoing severe hemorrhagic shock for 60 min and subsequent resuscitation. TN3.19.12 or placebo was given in a randomized and blinded manner either 60 min prior to shock induction, l min prior to resuscitation, or 15 min after the onset of resuscitation. The number of firmly adherent leukocytes in the livers of treated animals depended on the time of application of TN3.19.12. Leukocyte adhesion was significantly reduced when TN3.19.12 was given prior to shock induction or at the time of resuscitation and was less effective when administered after the onset of resuscitation. The results further confirm that TNF-α initiates very early pathological leukocyte adhesion in the liver 5 h following shock. Inhibition of leukocyte adhesion after shock, however, depends strongly on the time of TNF-α blocking. While TN3.19.12 prior to shock induction resulted in most effective attenuation, only very early treatment allowed limitation of posttraumatically increased leukocyte adhesion.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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