Altered Cytokines And Application Of Blood Purification In Multiple Organ Dysfunction Syndrome Resulted From Trauma

Object: A pig MODS model resulted from trauma was set up successfully with the complex factors of hemorrhagic shock, ischemia-reperfusion and endotoxin, and cytokines(VEGF, TNFa, IL-6 and IL-10) involved the mechanism of MODS was studied, as well as the influence of continuous blood purification (CBP) on major organ functions and cytokines. Methods: Sixteen pigs were randomly divided into two groups: MODS+CBP group (CBP group, n=6) and MODS group without CBP (MODS group, n=10). Among MODS group, by exanguinating 30～45% of total blood, mean arterial pressure decreased to 50～ 60mmHg for 2 hours. The 60% of the let blood, equilibrium liquid and colloid were transfused back into pigs for resuscitation in 1.5～2 hours, an hour later, 100μg/kg of endotoxin (E.coli O₅₅: B₅) was given via vein with 4～6 hours. High volume hemofiltration (HVHF) was performed an hour after endotoxin injection, lasting 16- 18 hours. Heart and pulmonary function were monitored continuously and supported necessarily, alive animals were sacrified in 7th days. Blood samples were collected at every time points for peripheral blood cells count, arterial blood gas, blood biochemical parameters and cytokines which were used to judge if MODS happened by comparing with themselves. The morbidity and mortality of MODS were calculated, and the pathomorphology changes of major organs were observed. Serum VEGF concentrations were determined in pigs with MODS, and the relationships with peripheral blood cells count, arterial blood gas, blood biochemical parameters, and inflammatory factors. The functions of major organs, serum cytokines levels and mortality between CBP group and MODSgroup were observed. Results: The morbidity and mortality of MODS were respectively 70% and 71.4%. The major feature in pathomorphology was inflammatory change non-specificially. Three organs failure was 57.1% and more than four was 42.9%. The incidence of single organ failure was 100% in both lung and gastrointestinal tract, and the high mortality happened in the heart failure and coagulation disorders. Serum concentrations of TNFa, IL-6 and IL-10 were significantly elevated after an hour of endotoxin injection. Serum VEGF levels increased in the periods of hemorrhagic shock and ischemia-reperfusion, then decreased after endotoxin introduction. The variance tendency of serum VEGF levels was negatively correlated with that of serum AST, ALT,TBIL and Cr, as well as serum ,TNFa ,IL-6, (TNFa + IL-6)/IL-10, which was positively correlated with PaO₂/FiO₂ and Plt counts. Serum VEGF levels in survivals were higher than deaths. In comparison to MODS group, PaO₂/FiO₂, AST, ALT and Cr of CBP group were higher, but TBIL and Plt were not obviously changed. Serum concentrations of TNFa, IL-6 and IL-10 decreased in the 3th～7th hour, then gradually increasing. The serum concentration of VEGF of CBP group was higher than MODS group after CBP. The mortality was significantly lower than MODS group. Conclusions: The MODS model analoguing the features of trauma could be successfully reproduced by complex factors, which has disequilibrium of SIRS/CARS. VEGF is closely related to organ dysfunction in MODS, and that SIRS could depress the expression of VEGF, and that VEGF may function as not a vascylar permeability factor, but a protective factor. Earlier CBP could improve the functions of major organs, low the serum concentrations of inflammatory factors, facilitate the expression of VEGF and reduce the mortality of MODS.