ORGAN DAMAGE IS PRECEDED BY CHANGES IN PROTEIN EXTRAVASATION IN AN EXPERIMENTAL-MODEL OF MULTIPLE ORGAN DYSFUNCTION SYNDROME

Our objective was to determine the serial evolution of Vascular permea bility as measured by protein extravasation in various organs during t he development of zymosan-induced multiple organ dysfunction syndrome (MODS). We evaluated the biodistribution of (111)Indium-labeled nonspe cific polyclonal immunoglobulin G (In-111-lgG). On days 2, 5, 8, and 1 2 after intraperitoneal challenge with 1 mg/g zymosan, mice were kille d. Heart, liver, spleen, kidneys, and the mesenteric lymph node comple x and tissue samples of muscle, ileum, and colon were dissected free a nd weighed. 24 h before death, 10 mu g of IgG labeled with 2 MBq In-11 1 was injected i.v. Relative organ weights (ROW), wet to dry weight ra tios (WDR), and a permeability index (PI) were calculated. ROW increas ed 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, an d colon Pi were the highest on day 2, followed by a decrease toward no rmal. Lung PI showed a triphasic course with peak Values at days 2 and 12. Mesenteric lymph node complex-Pl was continuously elevated. WDR ( tissue edema) and Pi (protein extravasation) have different courses in various organs. Most organs displayed an early increase in Pi, follow ed by a late decrease, white ROW (organ damage) was still increasing. it appears that organ damage is preceded by an increased protein extra vasation.