title: Inflammatory, coagulatory and circulatory responses to logarithmic increases in the endotoxin dose in the anaesthetised pig.
abstract: 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 microg/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-alpha, 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 < or = 1 microg/kg/h may be of advantage in experiments designed to study potential anti-endotoxin effects of experimental drugs or measures.
authors.affiliation: Section of Anaesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden. mlipcsey@eml.cc
authors.forename: Miklós
authors.initials: M
authors.lastname: Lipcsey
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Mats B
authors.initials: MB
authors.lastname: Eriksson
authors.forename: Jan
authors.initials: J
authors.lastname: Sjölin
mesh_terms: D000758:Anesthesia; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced*; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha