title: Plasma kallikrein generation in endotoxemia is abolished by ultra high doses of methyl-prednisolone: in vivo studies in a pig model.
abstract: Thirty-one healthy young pigs were studied to evaluate the effects of methylprednisolone sodium succinate (MP) on cellular, proteolytic, and hemodynamic parameters in normal and endotoxin-exposed animals. Fourteen animals served as controls, whereas 17 test animals received a continuous infusion of endotoxin, 0.01 mg/kg/3hr. Seven of the test animals and seven of the control group received a total of 200 mg/kg body weight over 5 hr of MP, 100 mg/kg as pretreatment before the endotoxin infusion was started. The administration of MP to control animals did not cause changes in the plasma kallikrein-kinin system, as determined with chromogenic peptide substrate assays. Only temporary effects, which normalized during the observation period, were seen in hemodynamic parameters. The pretreatment with MP significantly counteracted the increases in plasma kallikrein activity (KK) and the decreases in functional kallikrein inhibition capacity (KKI) seen after endotoxin infusion in untreated animals. Marked reductions in the number of circulating leukocytes and platelets were observed in untreated endotoxemia, together with increases in hematocrit. Furthermore, increases in pulmonary vascular resistance (PVR) and decreases in cardiac output (CO), left ventricular stroke work (LVSW), and mixed venous oxygen saturation (SvO2) ensued. The changes in circulating cells, PVR, and SvO2 were significantly counteracted by MP treatment, whereas changes in hematocrit, CO, and LVSW were only moderately improved.
authors.affiliation: Department of Surgery, Ullevaal Hospital, University of Oslo, Norway.
authors.forename: F
authors.initials: F
authors.lastname: Naess
authors.forename: O
authors.initials: O
authors.lastname: Roeise
authors.forename: J
authors.initials: J
authors.lastname: Pillgram-Larsen
authors.forename: T E
authors.initials: TE
authors.lastname: Ruud
authors.forename: J O
authors.initials: JO
authors.lastname: Stadaas
authors.forename: A O
authors.initials: AO
authors.lastname: Aasen
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood* / Q000633:toxicity; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D007610:Kallikreins / Q000097:blood*; D007705:Kinins / Q000097:blood; D008775:Methylprednisolone / Q000008:administration & dosage*; D013552:Swine; D014115:Toxemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D004731:Endotoxins; D007705:Kinins; D007610:Kallikreins; D008775:Methylprednisolone