title: Organ damage is preceded by changes in protein extravasation in an experimental model of multiple organ dysfunction syndrome.
abstract: Our objective was to determine the serial evolution of vascular permeability as measured by protein extravasation in various organs during the development of zymosan-induced multiple organ dysfunction syndrome (MODS). We evaluated the biodistribution of 111Indium-labeled nonspecific polyclonal immunoglobulin G (111In-IgG). On days 2, 5, 8, and 12 after intraperitoneal challenge with 1 mg/g zymosan, mice were killed. Heart, liver, spleen, kidneys, and the mesenteric lymph node complex and tissue samples of muscle, ileum, and colon were dissected free and weighed. 24 h before death, 10 micrograms of IgG labeled with 2 MBq 111In was injected i.v. Relative organ weights (ROW), wet to dry weight ratios (WDR), and a permeability index (PI) were calculated. ROW increased gradually until day 12. WDR also increased gradually in most organs. Lung WDR, however, initially increased, with a subsequent return to normal. Splenic WDR did not change over time. Liver, spleen, ileum, and colon PI were the highest on day 2, followed by a decrease toward normal. Lung PI showed a triphasic course with peak values at days 2 and 12. Mesenteric lymph node complex-PI was continuously elevated. WDR (tissue edema) and PI (protein extravasation) have different courses in various organs. Most organs displayed an early increase in PI, followed by a late decrease, while ROW (organ damage) was still increasing. It appears that organ damage is preceded by an increased protein extravasation.
authors.affiliation: Department of Surgery, University Hospital Nijmegen, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Nieuwenhuijzen
authors.forename: M F
authors.initials: MF
authors.lastname: Knapen
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: T
authors.initials: T
authors.lastname: Hendriks
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
authors.forename: R J
authors.initials: RJ
authors.lastname: Goris
mesh_terms: D000818:Animals; D001825:Body Fluid Compartments; D001831:Body Temperature; D001835:Body Weight; D002199:Capillary Permeability; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D015054:Zymosan / Q000633:toxicity
chemical_list: D011506:Proteins; D015054:Zymosan