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Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2004 (English)In: Critical care, ISSN 1364-8535, Vol. 8, no 1, p. 35-41Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2004. Vol. 8, no 1, p. 35-41
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95095OAI: oai:DiVA.org:uu-95095DiVA: diva2:169173
Available from: 2006-11-09 Created: 2006-11-09 Last updated: 2015-06-12Bibliographically approved
In thesis
1. Pathophysiological, Inflammatory and Haemostatic Responses to Various Endotoxaemic Patterns: An Experimental Study in the Pig
Open this publication in new window or tab >>Pathophysiological, Inflammatory and Haemostatic Responses to Various Endotoxaemic Patterns: An Experimental Study in the Pig
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig.

This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels.

Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia.

Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock.

Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function.

Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin.

Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. p. 69
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 197
Keyword
Anaesthesiology and intensive care, sepsis, animal model, cytokines, isoprostanes, endotoxic shock, pig, Anestesiologi och intensivvård
Identifiers
urn:nbn:se:uu:diva-7237 (URN)91-554-6709-1 (ISBN)
Public defence
2006-12-01, Hedstrandsalen, Ing 70, Akademiska sjukhuset, 751 85, UPPSALA, 13:15
Opponent
Supervisors
Available from: 2006-11-09 Created: 2006-11-09 Last updated: 2011-04-12Bibliographically approved

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Lipcsey, MiklósEriksson, Mats BLarsson, AndersSjölin, Jan

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