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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.
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  • 4
    ISSN: 1435-1420
    Keywords: Key words MOF – epidemiology – Goris score – Moore score – SOFA score ; Schlüsselwörter MOV – Epidemiologie – Goris-Score – Moore-Score – SOFA-Score
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Fragestellung: Interdisziplinäre Erfassung des Auftretens eines Multiorganversagens bei Patienten auf operativen und nicht-operativen Intensivstationen.¶   Methode: Prospektive, offene klinische Studie auf operativen und nichtoperativen Intensivstationen. Einschluss aller Patienten mit einer Behandlungsdauer über 48 Stunden auf einer Intensivstation in einem 3-Monatszeitraum. Tägliche Erhebung epidemiologischer Basisdaten und physiologischer Parameter zur Berechnung des SOFA-, Moore- und Goris-Scores. Analyse von Differenzwerten zwischen den Behandlungstagen und Korrelation mit dem Überleben hinsichtlich Aufnahmediagnosen und Fachgebieten.¶   Ergebnisse: 443 Patienten wurden eingeschlossen und 4880 Beobachtungstage dokumentiert. Es bestand ein Übergewicht an operativ behandelten Patienten (allgemeinchirurgisch (119 Pat.), unfallchirurgisch (163 Pat.), neurochirurgisch (82 Pat.)) gegenüber konservativ behandelten Patienten (Innere Medizin (49 Pat.), Neurologie (19 Pat.)). Überlebende wurden durchschnittlich 8 Tage und Verstorbene 6 Tage intensivmedizinisch behandelt. Die Gesamtmortalität betrug 17,3%. Fachspezifisch wiesen die nicht-operativen Fächer eine höhere Letalität auf mit einem höheren MOV-Score bei Aufnahme nach Goris als die operativ behandelten Patienten. Bei der Auswertung der Differenzwerte differenzierte der SOFA-Score am besten bezüglich Überleben und Versterben. Die Wertigkeit des Goris-Scores unterschied mit und ohne Verwendung der Parameter für ZNS und Gastrointestinaltrakt signifikant unterschiedlich zwischen überlebenden und verstorbenen Patienten.¶   Schlussfolgerung: Mit der vorliegenden Studie wurde ein erster interdisziplinärer intensivmedizinischer Basisdatensatz für Patienten 6 verschiedener Fachgebiete erhoben und verglichen. Es konnten fachgebietsspezifische Unterschiede bezüglich Struktur der Patientenkollektive und der Mortalität gezeigt werden. Diese haben Auswirkungen auf die Stratifizierung von Patientengruppen im Rahmen weiterer fachgebietsübergreifender Studien. Die klinische Einschätzung der Häufigkeit eines MOV als Todesursache und die der täglichen Zustandsänderung des Patienten im Rahmen seiner Erkrankung wurde von allen Scores nicht ausreichend widergespiegelt. Obgleich der SOFA-Score am zuverlässigsten über alle Fachbereiche zur Beurteilung des klinischen Verlaufs geeignet erscheint, ist die interdisziplinäre Weiterentwicklung eines fachübergreifenden Scores zur Beurteilung eines Multiorganversagens erforderlich.
    Notes: Summary Objective The aim of this prospective study was to describe a collective of patients with respect to the manifestation of multiple organ failure in operative and non-operative intensive care units.¶   Methods: Included were all patients treated longer than 48 hours in a participating intensive care unit. Basic epidemiologic data and physiological parameters were recorded and three different score values (SOFA, Moore and Goris scores) were calculated for each day in the intensive care unit and presented according to the particular specialty. A delta score value for each patient was calculated from the first and last recorded value and was compared to the outcome of the patient (survivor/non-survivor). With the Kohen-Kappa coefficient the daily change of the score value relating to an improvement or deterioration was referred to the clinical assessment. Further statistical analysis was performed with Mann-Whitney U test and by means of ANOVA.¶   Results: 443 patients were included and 4880 observation days were recorded. There was an over-representation of operative patients (general surgery (119 pat.), trauma surgery (163 pat.), neurosurgery (82 pat.)) compared to non-operative patients (medicine (49 pat.), neurology (19 pat.)). Survivors stayed 8 and non-survivors 6 days in the intensive care unit. Overall mortality was 17.3%.¶   Non-operative specialties had a higher mortality with a significantly higher Goris multiple organ failure score on admission for neurologic patients and a higher Goris multiple organ failure score for medical patients (not significant) compared to operative patients.¶   The delta SOFA score value is the most powerful to indicate survival or death compared to the other two delta scores. The Goris score on admission produces statistically significant differences concerning survivors and non-survivors even without the gastrointestinal and central nervous system, but is unreliable considering the delta score.¶   Conclusion: In the present investigation, a basic data set for patients from six different medical specialties were collected and compared. Faculty-specific differences between sets of patients and mortality were shown. This will have consequences for stratifying groups of patients for further interdisciplinary investigation. Clinical assessment of the incidence of multiple organ failure and clinical assessment of changes in daily multiple organ failure status were poorly mirrored by all scores under surveillance. Considering delta score values, the SOFA score is the most reliable score for interdisciplinary description of survival or non-survival. Although the SOFA score seems most reliable for describing a patient‘s clinical course, there is a need for the development of a comprehensive, interdisciplinary score for assessment of multiple organ failure.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Schädel-Hirn-Trauma ; Polytrauma ; Entzündungsmediatoren ; Key words Severe head trauma ; Polytrauma ; Inflammatory mediators
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Isolated severe head trauma (SHT) or SHT in combination with multiple injuries are important factors for the prognosis of morbidity and mortality in patients suffering from the consequences of accidents. The prognosis mainly depends on the presence of primary mechanic brain injury and the development of secondary brain damage. Causes for the development of secondary brain damage are the intracranial space demand after traumatic injury and edema formation which may result in iscemia, as well as inflammatory processes. Both isolated SHT and polytrauma with or without brain damage may result in a systemic inflammatory response syndrome (SIRS) due to the synthesis of cytokines and other inflammatory mediators which may cause a single or multiple organ failure (MOF). Often the organism is able to survive isolated traumatic injuries and functional disturbances, but in combination or cumulation they may be lethal. The hypermetabolism after SHT is often regarded as an interaction between the central nervous system and the whole organism by the activation of the neuroendocrine axis. In contrast to the consequences of SHT for the whole organism, multiple injuries after polytrauma may affect brain functions, such as the shock dependent disturbance of the brain perfusion accompanied by brain hypoxia which may lead to an aggravated prognosis. Moreover, coagulation, metabolism and fracture healing are influenced by the onset of SIRS as well. Our knowledge about the bidirectional inflammatory interaction between brain and whole organism is still limited. In this context, the effects of secondary surgical interventions which may additionally stress a traumatized body have to be considered and are the subject for actual clinical discussions and experimental studies. This article tries to summarize some important aspects on this topic.
    Notes: Zusammenfassung Das isolierte oder mit weiteren Verletzungen kombinierte Schädel-Hirn-Trauma (SHT) ist ein Hauptprognosefaktor für Morbidität und Mortalität nach einem Unfallereignis. Die Prognose des Patienten ist sowohl von der primären, mechanischen Hirnschädigung als auch von der Entwicklung sekundärer Hirnschäden abhängig. Als Ursachen einer sekundären Hirnschädigung werden neben der intrakraniellen Raumforderung aufgrund posttraumatischer Blutungen und Ödembildungen, sowie der daraus resultierenden Ischämie, Entzündungsprozesse diskutiert. Sowohl beim isolierten SHT als auch nach Polytrauma mit und ohne Hirnschädigung kann eine inflammatorische “Systemreaktion” (SIRS) unter der Beteiligung von Zytokinen und anderen Entzündungsmediatoren zu einem Ein- oder Multiorganversagen (MOF) führen. Dabei sind einzelne Verletzungskomponenten und Funktionsstörungen meistens überlebbar, können jedoch in Ihrer Kombination und Kumulation tödlich enden. Hypermetabolische Zustände nach einem SHT werden auch als Interaktionen des ZNS mit dem Gesamtorganismus unter Beteiligung der neuroendokrinen Achse aufgefaßt. Diesen Auswirkungen eines SHT auf den übrigen Organismus ist der Einfluß multipler Verletzungen eines polytraumatisierten Verletzten auf die Hirnfunktion gegenüberzustellen, wobei schockbedingte Perfusionsstörungen eine prognoselimitierende Hypoxie des Gehirns verursachen können. Darüber hinaus beeinflußt die generalisierte “Ganzkörperentzündungsreaktion” Blutgerinnung, Stoffwechsel und Frakturheilung. Die Kenntnisse der traumainduzierten, bidirektionalen, inflammatorischen Interaktionen zwischen Gehirn und Gesamtorganismus, sowie der Einfluß der derzeit angewendeten Therapiemaßnahmen sind bisher noch unzureichend und bedürfen weiterer Aufklärung. Letztendlich muß aus dieser Sicht auch die Wahl des richtigen Zeitpunktes für sekundäre Eingriffe, die nicht unmittelbar der Lebenserhaltung dienen und zu einer zusätzlichen Belastung des Patienten durch das Operationstrauma führen, überdacht werden. Diese Arbeit versucht wichtige Aspekte auf diesem Gebiet zusammenzufassen.
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  • 7
    ISSN: 1432-2277
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 8
    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.
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  • 9
    ISSN: 1432-2277
    Keywords: Pancreas transplantation, in the pig ; Experimental pancreas transplantation, pig, anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A major problem in pancreatic autotransplantation is the vascular supply of the left segment, which serves as the graft. We therefore examined the arterial blood supply of the epigastric organs in 36 German landrace pigs. In 19 pigs (anatomical variation 1) there was a pancreatic branch of the splenic artery supplying the left segment. After splenectomy the splenic artery could be used as the graft-supplying vessel. In 14 pigs (anatomical variation 2) the arterial branch for the left segment was the first branch out of the hepatic artery distal to the coeliac trunk. In these cases a splenohepatic bypass was performed to ensure delivery of the blood to the epigastric organs. Thereafter, the proximal part of the hepatic artery could be used as the vessel supplying the graft. The left segment could not be used for autotransplantation in 3 pigs (anatomical variation 3) because of the atypical vascular supply. During the 6-month observation period, no malfunction of the epigastric organs was evident.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 372 (1987), S. 944-945 
    ISSN: 1435-2451
    Keywords: Pancreatic autotransplantation ; Temporary duct occlusion ; Fibrin sealant ; Aprotinin ; Pankreasautotransplantation ; Temporäre Gangblockade ; Fibrinocclusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach Pankreaskopfresektionen bzw. nach Pankreasautotransplantationen am Schwein wurde der Pankreasgang mit einem modifizierten Fibrinkleber verschlossen. Die Fibrinocclusion erzeugt keine Pankreatitis. Die exokrine Akivität des Organs kann bis zu drei Tagen unterbrochen werden. Diese Zeitspanne genügt für ein ungestörtes Einheilen von Pankreasanastomosen. Langzeitbeobachtungen zeigen eine ungestörte Funktionstüchtigkeit des endokrinen und des exokrinen Pankreas. Diese neue Technik verbindet die Vorteile der Gangocclusion mit denen der Gangdrainage.
    Notes: Summary The pancreatic duct of pigs was occluded with a modified fibrin glue following resection of the head of the pancreas or autotransplantation of the left pancreatic segment. Occlusion with liquid fibrin glue did not induce pancreatitis. Following the injection, the exocrine activity was interrupted for 3 days. This allowed time for healing of the pancreas anastomoses to the gut to occur. Three months later, all animals had normal exocrine and endocrine activities. This new technique combines the advantages of permanent duct occlusion with those of duct drainage.
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