title: A new dynamic porcine model of meningococcal shock.
abstract: The objective of this study was to establish a porcine analog of human meningococcal sepsis for pathophysiological investigations and possible future therapy in severe sepsis. Heat-killed Neisseria meningitidis was continuously infused in sublethal concentrations into 10 anesthetized 30-kg pigs (sepsis group). The dose was doubled every 30 min. Six pigs received saline only (control group). The changes described in the succeeding paragraphs were observed in the sepsis group but not in the control group. MAP was aimed to be kept normal by fluid infusion but declined after 3 h in parallel with a decrease in systemic vascular resistance. Pulmonary arterial pressure increased considerably after 30 to 45 min. A massive plasma extravasation was shown by increased hematocrit and a 50% reduction in plasma albumin content. Fluid accumulated in lungs, muscles, and jejunum, as shown by increased wet-dry ratios. Peak inspiratory pressures and fraction of inspired oxygen had to be increased. The cytokines TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and IL-12 increased markedly. Neutrophils fell to zero-levels, and platelets were markedly reduced. Thrombin-antithrombin complexes increased notably after 120 min. This is the first large animal model of sepsis using whole Neisseria meningitidis. The model simulates well central aspects of human meningococcal sepsis and could be used for future interventional studies.
authors.affiliation: Department of Anesthesiology, Norland Hospital, Bodø, Norway. erikwn@fagmed.uit.no
authors.forename: Erik Waage
authors.initials: EW
authors.lastname: Nielsen
authors.forename: Bernt Christian
authors.initials: BC
authors.lastname: Hellerud
authors.forename: Ebbe Billmann
authors.initials: EB
authors.lastname: Thorgersen
authors.forename: Albert
authors.initials: A
authors.lastname: Castellheim
authors.forename: Anne
authors.initials: A
authors.lastname: Pharo
authors.forename: Julie
authors.initials: J
authors.lastname: Lindstad
authors.forename: Tor Inge
authors.initials: TI
authors.lastname: Tønnessen
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008589:Meningococcal Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D009345:Neisseria meningitidis / Q000502:physiology; D011897:Random Allocation; D012772:Shock, Septic / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12