Organ damage is preceded by changes in protein extravasation in an experimental model of multiple organ dysfunction...

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.