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Michael Groeger,
Jose Matallo,
Oscar McCook,
Florian Wagner,
Ulrich Wachter,
Olga Bastian,
Saskia Gierer,
Vera Reich,
Bettina Stahl,
Markus Huber-Lang,
Csaba Szabó,
Michael Georgieff, Peter Radermacher,
Enrico Calzia,
Katja Wagner
[show abstract]
[hide abstract]
ABSTRACT: Previous studies suggest that sulfide-induced inhibition of cytochrome c oxidase (cCox) and, consequently, the metabolic and toxic effects of sulfide are less pronounced at low body temperature. Because the temperature-dependent effects of sulfide on the inflammatory response are still a matter of debate, we investigated the impact of varying temperature on the cCox excess capacity and the mitochondrial sulfide oxidation by the sulfide-ubiquinone oxidoreductase in macrophage-derived cell lines (AMJ2-C11 and RAW 264.7). Using an oxygraph chamber, the inhibition of mitochondrial respiration was measured by stepwise titrations with sulfide and the nonmetabolizable cCox inhibitor sodium azide at 25°C and 37°C. Using the latter of the two inhibitors, the excess capacity of the cCox was obtained. Furthermore, we quantified the capacity of these cells to withstand sulfide inhibition by measuring the amount required to inhibit respiration by 50% and 90% and the viability of the cells after 24-h exposure to 100 ppm of hydrogen sulfide. At low titration rates, the AMJ2-C11 cells, but not the RAW 264.7 cells, increased their capacity to withstand exogenously added sulfide. This effect was even greater at 25°C than at 37°C. Furthermore, only the AMJ2-C11 cells remained viable after sulfide exposure for 24 h. In contrast, only in the RAW 264.7 cells that an increase in cCox excess capacity was found at low temperatures. In macrophage-derived cell lines, both the excess capacity of cCox and the efficiency of sulfide elimination may increase at low temperatures. These properties may modify the effects of sulfide in immune cells and, potentially, the inflammatory response during sulfide exposure at different body temperatures.
Shock (Augusta, Ga.) 07/2012; 38(4):367-74. · 2.87 Impact Factor
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F. Simon,
E. Jäger, P. Radermacher,
E. Calzia,
U.B. Brückner,
M. Thiere,
A. Oberhuber,
J. Kick,
K.H. Orend,
L. Sunder-Plassmann,
H. Schelzig
[show abstract]
[hide abstract]
ABSTRACT: Rekonstruktionen im thorakoabdominalen Abschnitt der Aorta ziehen mehr oder weniger akzentuierte Ischämie/Reperfusion-Sequenzen
nach sich. Deren Folgen sind bestenfalls eine vorübergehende Funktionsstörung des abhängigen Gefäßabschnitts. Klinischer Alltag
bei diesen ausgedehnten Eingriffen ist die Induktion einer systemischen Inflammation. Im Extremfall kann es zu einem dauerhaften
Funktionsverlust eines oder mehrerer Organe kommen. Neben individuellen Konditionen ist die Ausprägung dieser Sequenz in hohem
Masse zeitabhängig. Die aus klinischer Sicht empfindlichsten Organe scheinen hier Neurone und tubuläre Nierenzellen zu sein.
Diese Zusammenhänge führten zu unterschiedlichsten perioperativen Maßnahmen. Die grundlegende Strategie ist hier entweder
die Ischämie/Reperfusion zu vermeiden (z.B. arterioarterieller Shunt, extrakorporaler Kreislauf) oder abzukürzen (z.B. „branched“
Stentgraft, Hybridverfahren, Vortex, Clamp-repair mit sequenzieller Ausklemmung).
Betrachtet man allein die deutschsprachigen Beiträge der letzten Jahrestagungen der Gefäßchirurgie in Bern 2007 und Dresden
2008, so könnte das Vorgehen in den einzelnen Kliniken uneinheitlicher nicht sein. Diese geringe Standardisierung weißt möglicherweise
darauf hin, dass das Problem „zu multifaktoriell“ ist und/oder wesentliche Aspekte in der Pathophysiologie nicht ausreichend
erfasst werden.
Gewebehypoxie und Funktionsverlust sind klassische Folgen unterschiedlicher Schockformen (Polytrauma, septischer Schock, Hämorrhagie).
Der entscheidende Unterschied zur Ischämie/Reperfusion-Sequenz in der Gefäßchirurgie ist jedoch, dass das auslösende Moment
zeitlich genau zu terminieren ist. Daraus ergibt sich die Möglichkeit, regulierend in dieses Geschehen einzugreifen, wenn
es in seinem Ablauf verstanden wird. Ohne diese Idee der Konditionierung wäre die moderne Transplantationsmedizin nicht möglich.
Hier hat die therapeutische Beeinflussung der Ischämie/Reperfusion-Phänomene zentrale Bedeutung.
Die Therapie der Erkrankungen der Aorta ist eine interdisziplinäre Herausforderung. Daher erfolgte 1999 an der Universität
Ulm die Gründung einer Arbeitsgruppe aus Anästhesisten und Gefäßchirurgen, mit dem Ziel, die Pathophysiologie und Therapie
der Ischämie/Reperfusion-Phänomäne systematisch zu erforschen. Der vorliegende Artikel zeigt einen Teil der bisher geleisteten
Arbeit, um einen Ausblick auf zukünftige Projekte zu gewähren.
Reconstructions in the thoraco-abdominal section of the aorta are nearly always accompanied by accentuated ischemia and reperfusion
sequences to varying degrees. The consequences are at best a temporary functional disturbance of the affected section. The
normal clinical result of these extensive operations is induction of systemic inflammation, which in extreme cases can result
in permanent loss of function of one or more organs. In addition to individual-specific conditions the extent of this sequence
is highly time-dependent. The most sensitive organs from a clinical point of view seem to be neurons and renal tubules. These
relationships have led to very different operative measures. The basic strategy is either to avoid ischemia/reperfusion (e.g.
arterio-arterial shunt, extracorporeal circulation) or to shorten (e.g. branched stent graft, hybrid procedures, vortex, clamp
repair with sequential clamping). If only the articles in German from the last two congresses on vascular surgery in Bern
2007 and Dresden 2008 are taken into consideration, the approaches of the individual hospitals could not be more inconsistent.
This low level of standardization possibly indicates that the problem is too multifactorial and/or that essential aspects
of the pathophysiology have not been sufficiently considered.
Tissue hypoxia and loss of function are classical consequences of various forms of shock (e.g. multiple trauma, septic shock,
hemorrhaging). The deciding difference to an ischemia/reperfusion sequence in vascular surgery is, however, that the trigger
moment in time can be exactly determined. From this the possibility arises to intervene in this event if its course has been
comprehended. Without this concept of conditioning modern transplantation medicine would not be possible. In this situation
the therapeutic influence on ischemia/reperfusion phenomena is of pivotal significance.
Treatment of diseases of the aorta is an interdisciplinary challenge. For this reason a working group of anesthetists and
vascular surgeons was founded at the University of Ulm in 1999 in order to systematically carry out research on the pathophysiology
and therapy of ischemia/reperfusion phenomena. This article presents part of the work already achieved to allow a perspective
on future projects.
Gefässchirurgie 04/2012; 14(1):16-23. · 0.24 Impact Factor
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Critical Care 04/2012; 4:1-2. · 4.93 Impact Factor
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Critical Care 04/2012; 4:1-2. · 4.93 Impact Factor
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Critical Care 04/2012; 6:1-2. · 4.93 Impact Factor
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Critical Care 04/2012; 4:1-1. · 4.93 Impact Factor
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Critical Care 04/2012; 4:1-2. · 4.93 Impact Factor
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Critical Care 04/2012; 4:1-2. · 4.93 Impact Factor
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Critical Care 04/2012; 4:1-2. · 4.93 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Achievement of a mean blood pressure (MBP) target is one of the hemodynamic goals to ensure an adequate blood perfusion pressure in critically ill patients. Arterial catheter allows for a continuous and precise monitoring of arterial pressure signal. In addition to giving a precise MBP monitoring, analysis of the blood pressure wave provides information that may help the clinician to interpret hemodynamic status. The interpretation of BP wave requires the understanding of simple principles. In this review, we first discuss the physiological mechanism responsible for arterial pressure generation. We then emphasize the interpretation of the static indexes and the dynamic indexes generated by heart-lung interactions derived from arterial pressure wave. Finally, we focus on MBP value as a therapeutic target in critically ill patients. We discuss the recommended target MBP value by reviewing available data from experimental and clinical studies.
European Journal of Intensive Care Medicine 03/2011; 37(3):411-9. · 5.17 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: This study tested the hypothesis that propofol is associated with a higher hepatic blood flow in humans compared with desflurane. Using a cross over study design, 10 patients received first propofol and then desflurane, and a further 10 patients received desflurane and then propofol. Blood flow index in the right and middle hepatic veins, stroke volume index and cardiac index were assessed by transoesophageal echocardiography. Mean arterial blood pressure, stroke volume index and cardiac index were the same in both groups. Propofol was associated with significantly greater blood flow index in the right hepatic vein (median (IQR [range]) 199 (146-237 [66-388]) vs. 149 (112-189 [42-309]) ml.min(-1).m(-2); p = 0.005) and middle hepatic vein (150 (122-191 [57-341]) vs. 125 (92-149 [47-362]) ml.min(-1).m(-2); p < 0.001) compared with desflurane. In routine clinical conditions, propofol anaesthesia was associated with significantly greater hepatic blood flow than desflurane anaesthesia.
Anaesthesia 11/2010; 65(11):1085-93. · 2.96 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Endotoxemia is a crucial factor in the pathogenesis of sepsis. Elimination of endotoxin is aimed at the reduction of sepsis-related morbidity and lethality. The objective of this study was to examine the impact of an endotoxin adsorber on hemodynamics, O(2) exchange and metabolism during resuscitated porcine endotoxemia.
Twenty pigs were randomized into 2 intervention groups (n = 7 each) and 1 control group (n = 6). Endotoxemia was induced by continuous intravenous application of lipopolysaccharide for 8 h. Adsorber therapy was started at the same time as the induction of endotoxemia or 2 h later. An extracorporeal hemoperfusion device using immobilized human serum albumin for endotoxin adsorption was used.
Hemodynamic, metabolic and acid-base parameters, as well as the kinetics of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-alpha, were characteristic for endotoxic shock. Endotoxin plasma levels were low (arterial, hepatic and portal vein). None of the parameters were significantly influenced by the adsorber system.
Despite typical clinical signs of endotoxemia, the adsorber system had no significant effect on hemodynamic, metabolic and acid-base parameters during endotoxic shock. The reasons for the absence of an effect are elusive; however, failure of the method per se or exceeded capacity of the adsorber cannot be excluded.
European Surgical Research 06/2009; 43(1):53-60. · 0.93 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Hydrogen sulfide (H2S), a gas with the characteristic odor of rotten eggs, is known for its toxicity and as an environmental hazard [1–5]. Recently H2S has been recognized as a signaling molecule of the cardiovascular, inflammatory and nervous systems. Alongside with nitric
oxide (NO) and carbon monoxide, it is now referred to as the “third endogenous gaseous transmitter” [6]. Inhalation of gaseous H2S and administration of compounds that donate H2S have been studied in various models of ischemia-reperfusion and circulatory shock [7–24].
12/2008: pages 171-179;
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[show abstract]
[hide abstract]
ABSTRACT: Sepsis is a complex syndrome characterized by an uncontrolled and deregulated systemic inflammatory response to infection.
This is mediated by a broad spectrum of endogenous mediators whose actions result in multiple organ dysfunction distant from
the original focus of infection. The kidney is a common ‘victim organ’ of various insults in critically ill patients. Sepsis
and septic shock are the dominant causes of acute kidney injury (AKI), accounting for nearly 50 % of episodes of acute renal
failure [1]. The incidence of AKI in sepsis increases proportionally with the severity of sepsis, with AKI developing in 19 % of patients
with sepsis, 23 % of those with severe sepsis, and 51 % of patients with septic shock [2]. The mortality of sepsis patients with co-existing acute renal failure reaches 70 %, thereby outstripping that of patients
with other causes of AKI [3]. Interestingly, even relatively minor increments in serum creatinine levels coincide with markedly increased morbidity and
mortality [4], highlighting the potentially important role of kidney dysfunction during the natural history of critical illness. However,
the precise understanding of the multifactorial mechanisms of sepsis-induced AKI that would allow the development of new therapeutic
strategies to prevent AKI or to hasten its recovery remains a mystery. Here, we review the most recent advances in the understanding
of the molecular mechanisms and pathophysiology of sepsis-induced AKI, focusing on renal hemodynamic and microvascular changes
and on the importance of a rapidly evolving proteomics approach to evaluating sepsis-induced kidney dysfunction.
12/2007: pages 568-578;
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[show abstract]
[hide abstract]
ABSTRACT: Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases such as carbon monoxide and cyanide. As a wide variety of synthetic materials is used in buildings, such as insulation, furniture, carpeting, electric wiring covering as well as decorative items, the potential for poisoning from inhalation of products of combustion is continuously increasing. The present review describes the pathophysiologic effects from smoke inhalation injury as well as strategies for emergency treatment on scene and in the intensive care setting.
Der Anaesthesist 10/2006; 55(9):980-2, 984-8. · 0.99 Impact Factor
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Shock 09/2006; 26(4):35. · 2.85 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Die Mehrzahl der tdlichen Brandunflle ist nicht auf Brandwunden, sondern auf die Inhalation toxischer Gase whrend des Verbrennungsvorgangs zurckzufhren. Feuer erzeugt eine komplizierte toxische Umgebung durch Hitze, Sauerstoffverbrauch und die Entstehung toxischer Gase, wie Kohlenmonoxid und Zyanid. Die zunehmende Nutzung synthetischer Baumaterialien in Gebuden, Mbeln, Teppichbden, elektrischen Kabelstrngen und Dekorationen erhht das potenzielle Risiko der Inhalation toxischer Brandgase. Dieser bersichtsartikel beschreibt die pathophysiologischen Prozesse nach Inhalationsverletzungen, die durch toxische Substanzen und Chemikalien in Rauchgasen ausgelst werden, sowie Strategien fr die notrztliche Versorgung an der Unfallstelle und die weiterfhrende intensivmedizinische Behandlung.Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases such as carbon monoxide and cyanide. As a wide variety of synthetic materials is used in buildings, such as insulation, furniture, carpeting, electric wiring covering as well as decorative items, the potential for poisoning from inhalation of products of combustion is continuously increasing. The present review describes the pathophysiologic effects from smoke inhalation injury as well as strategies for emergency treatment on scene and in the intensive care setting.
Der Anaesthesist 08/2006; 55(9):980-988. · 0.99 Impact Factor
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Intensive Care Medicine 02/2006; 32(1):21-3. · 5.40 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Taken together, proteins of the antioxidant defense system can be damaged by oxidative stress, and, in fact, there is evidence
that they are even specifically susceptible. The oxidative loss of protein moiety is partially compensated by de novo synthesis. This compensatory mechanism complicates any attempt to relate mRNA profiles assessed by cDNA technology or protein
expression profiles assessed by 2D-gel electrophoresis to the functionally active protein content. The dynamic cellular response
with sepsis can only be revealed by disentangling the enormously complex response at the protein level. The only method able
to deliver appropriate information is a proteomic platform based on differential and quantitative approaches, which is extended
by synthesis or turnover measurements.
Our ultimate aim is to use this dynamic approach:
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to understand the complex interaction between the various elements of the defense system;
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to define a set of measurements necessary to characterize the various conditions of the system; and
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to develop a tool box to evaluate the efficacy of therapeutic measures intended to support the defense system.
12/2005: pages 23-34;
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12/2004: pages 19-32;
