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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
    Der Anaesthesist 45 (1996), S. 976-992 
    ISSN: 1432-055X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Lernziele Die komplexen pathophysiologischen Vorgänge und das akute klinische Bild eines hämorrhagischen Schockgeschehens stellen hohe Anforderungen an die präklinische und klinische ärztliche Versorgung. Neben den sympathoadrenergen Kompensationsmechanismen sind die Störungen der Mikrozirkulation und die Umstellung des Zellstoffwechsels für die Entstehung einer systemischen Entzündungsreaktion bis hin zum Multiorganversagen bedeutsam. Diese Übersicht soll folgende Inhalte vermitteln: — Pathophysiologe des hämorrhagischen Schocks — Präklinische und klinische Diagnostik — Aktuelle notfall- und intensivmedizinische Behandlungskonzepte — Klinische Versorgungsstrategie
    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: 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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  • 4
    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
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  • 5
    ISSN: 1432-2277
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2277
    Keywords: Liver transplantation ; rat ; N-acetylcysteine ; N-acetylcysteine ; rat ; liver transplantation ; Preservation ; rat liver ; N-acetylcysteine ; Microcirculation ; N-acetylcysteine ; liver preservation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The application of radical scavengers reduces reperfusion injury of liver grafts despite the natural occurrence of cellular defense mechanisms enabling the cell to tolerate moderate oxidant stress without further cell damage. The glutathione peroxidase mechanism of the liver serves to reduce hydroxyl radical-induced lipid peroxidation by releasing reduced glutathione from intracellular stores. There is evidence that the application of cysteine-providing aminoacids for glutathione synthesis could maintain or even increase liver glutathione. Therefore, the purpose of this study was to evaluate the effect of N-acetylcysteine (NAC) on oxidative stress-induced reperfusion injury after liver transplantation. This was done by applying intravital microscopy. Livers from female Sprague-Dawley rats weighing 220–260 g were stored for 20 h in University of Wisconsin (UW) solution and transplanted orthotopically using the cuff technique. Donors were given 150 mg/kg body weight NAC i. v. or placebo in a blind, random fashion 6 h prior to harvesting, followed by two injections of 50 mg/kg body weight, 4 and 2 h before explantation. In additional experimental groups, recipients were given a bolus of 83 mg/kg body weight NAC or placebo at the beginning of the recipient operations, 1 min prior to reperfusion, and 60 min after surgery. Ninety minutes after transplantation, intravital microscopy was applied and five liver lobules were recorded for 30 s after injection of acridine orange, a fluorescent leukocyte marker. Sinusoidal perfusion, sinusoidal width, and leukocyte adhesion, as well as reduced and oxidized glutathione, were determined in all livers. Neither microcirculatory disturbance nor leukocyte adhesion was less, nor was the liver glutathione in the recipient groups pretreated or treated with NAC greater than that in rats receiving the placebo. Moreover, liver glutathione was significantly decreased in livers from donors pretreated with NAC. In conclusion, the application of NAC as a pretreatment for donors and as treatment for recipients, respectively, failed to reduce early microvascular failure after liver transplantation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 383 (1998), S. 199-208 
    ISSN: 1435-2451
    Keywords: Key words Polytrauma ; Pathophysiology ; Mediator ; Inflammation ; Multiple organ failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Multiple trauma induces an inflammatory response syndrome of the whole body that is triggered by (a) hemorrhage inducing an ischemia/reperfusion (I/R) syndrome and (b) fractures or organ contusions inducing tissue-repair processes. I/R injury generates oxyradical/proteolytic metabolites and adhesion molecules, while tissue and endothelial injury directly stimulate complement, coagulation and kinin pathways. Membrane-derived phospholipase A2 and lipid mediators potentiate cellular interactions and increase microvascular permeability. The tissue-repair process mediates macrophage/monocyte and T-cell activation which releases pro- and anti-inflammatory cytokines. Mediator action follows a “three-level model”, proposing that depending on the degree of traumatic injury cellular and humoral responses may spread from a cellular to an organ and then a systemic level. The systemic response can result in a severe immunological dys-homeostasis that potentially hazards the survival of the trauma patient by uncontrollable cellular dysfunction, appearing clinically as multiple organ-dysfunction syndrome. Blood-mediator concentrations often parallel the inflammatory process; initially, high levels of cytokines are followed by severe organ dysfunction. However, interpretation of these data remains difficult due to distinct beneficial or detrimental effects of mediators on the different levels of inflammation and missing prognostic threshold values, indicating a risk of adverse effects. Future studies must determine pro- and anti-inflammatory mediators directly, during the intensive care therapy, and evaluate their clinical relevance prospectively for the different levels of inflammation at local and systemic sites.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-2568
    Keywords: pancreas microcirculation ; blood flow ; secretin ; cholecystokinin ; epifluorescent microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using epifluorescent microscopy, we investigated the dynamic changes in pancreatic microcirculationin vivo after bolus administration of secretin (SEC) (0.1–10.0 µg/100 g body wt) and cholecystokinin-octapeptide (CCK-8) (0.005–1.2 µg/100 g body wt) in pentobarbital-anesthetized rats. Pancreatic capillary red cell velocity as a monitor for pancreatic capillary blood flow was measured in 1-min intervals from 2 min prior to 8 min following bolus infusion of SEC or CCK-8. Physiological concentrations of SEC did not increase pancreatic capillary blood flow. However, pharmacological SEC concentrations induced a dose-dependent increase in pancreatic capillary blood flow (to 162±19% of baseline;P〈0.05), due to an increase in blood flow velocity (to 153±18% of baseline;P〈0.05). In contrast, bolus administration of physiological CCK-8 concentrations, which have been proven to stimulate enzyme secretion, induced a transient and dose-dependent increase in pancreatic capillary blood flow (to 235±24% of baseline;P〈0.05), due to an increase in blood flow velocity (to 184±13% of baseline;P〈0.05) and capillary diameters (+0.63 ± 0.15 µm;P〈0.05).
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of trauma 25 (1999), S. 3-3 
    ISSN: 1615-3146
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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