This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Lipcsey, M. Articles by Sjölin, J. Search for Related Content PubMed PubMed Citation Articles by Lipcsey, M. Articles by Sjölin, J. Social Bookmarking                         What's this?

Inflammatory, coagulatory and circulatory responses to logarithmic increases in the endotoxin dose in the anaesthetised pig

Section of Anaesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden, mlipcsey{at}eml.cc

Anders Larsson

Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

Mats B. Eriksson

Section of Anaesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden

Jan Sjölin

Section of Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

Although porcine intravenous endotoxin shock models are widely employed in experimental sepsis, endotoxin dose-effect studies are scarce. Our primary aim was to establish the dose response to increasing endotoxin doses in inflammatory, coagulatory and haemodynamic effect variables, as well as to determine the optimal time point for assessment in a pig model. A secondary aim was to study pathophysiological covariations between the different responses. Twenty anaesthetised piglets received endotoxin intravenously in doses of 0.063 (n = 3), 0.25 (n = 3), 1.0 ( n = 3), 4.0 (n = 3), 8 (n = 3) and 16 µg/kg/h (n = 2). In addition, non-endotoxin piglets constituted a control group (n = 3). Physiological variables were registered and blood samples analysed for TNF-, IL-6, leukocyte, platelet and haemoglobin concentrations hourly for 6 h. Increases in the endotoxin dose induced significant log—log cytokine responses as well as log—linear leukocyte and platelet responses. Significant log—linear responses were observed for circulatory parameters, plasma leakage, hypoperfusion and pulmonary compliance. Significant covariations in the responses were noted. In conclusion, there were log—log or log—linear responses to endotoxin suggesting a greater effect of a given dose at lower pre-existing endotoxin concentrations and lower doses of 1 µg/kg/h may be of advantage in experiments designed to study potential anti-endotoxin effects of experimental drugs or measures.

Key Words: Animal model • cytokines • dose-response relationship • endotoxic shock • pig

Journal of Endotoxin Research, Vol. 12, No. 2, 99-112 (2006)
DOI: 10.1177/09680519060120020601


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?