| Multiple organ dysfunction syndrome (MODS) is the most frequent cause of death in patients admitted to intensive care units. Severe sepsis and septic shock are the primary causes of MODS and develop as a result of the host response to infection of Gram-negative and Gram-positive bacteria. Infectious sepsis and noninfectious systemic inflammatory response syndrome (SIRS) encompass a complex mosaic of interconnected events. The activation and amplification of the immune response in SIRS/MODS appears to depend on the production and release of pro-inflammatory/ anti-inflammatory, water-soluble small and middle molecules. Attenuating the systemic effects of these inflammatory mediators is a logical goal of adjuvant therapy in SIRS/MODS. Unfortunately, the results of targeting single mediators during established septic shock have been disappointing. Therapies aiming at simultaneously reducing the plasma concentration of several circulating inflammatory mediators may prove more effective. Continuous haemofiltration is one of these therapies."Standard" haemofiltration (exchange rates of 1-2L/h) has often improved cardiopulmonary function in septic patients independent of fluid balance but has failed to achieve adequate mediator removal. Accordingly, an increase in the rate of plasma water exchange has been proposed and is supported by initial animal experiments. High-volume haemofiltration (6L/h) in porcine and canine endotoxic shock improves arterial blood pressure and cardiac output.All of the known mediators of SIRS/MODS have the potential to modulate apoptosis in organ tissues and endothelial cells. The role that apoptosis plays in sepsis syndromes and in the development of MODS has not been adequately explored, but there is rapidly developing evidence to suggest that increased apoptotic processes may play a determining role in the outcome to sepsis syndromes. In particular, increased apoptosis, particularly in lymphoid tissues and potentially in some parenchymal tissues from solid organs, may contribute to the sepsis-associated MODS and can be a potential therapeutic target for intervention. Direct apoptotic organ injury and the immune suppression secondary to apoptotic losses in T cell, B cell, and NK cell populations may contribute significantly to the risk of secondary opportunistic infections. Therapeutic efforts at modulating the apoptotic response, particularly by interfering with cell signaling pathways that lead to caspase-mediated apoptosis, represent an attractive therapeutic target for the septic patient. The purpose of the present study is to explore the effect of HVHF on the clearence of circulating cytokines, and the relevant downstream effect of cytokines: apoptosis. Examination of the mechanisms of programmed death of vital organ tissue cells or their respective inflammatory cells might provide insight as to why, despite aggressive vital organ support in ICUs and even in the absence of infection, patients with SIRS develop multiple organ dysfunction.To better understand the pathogenesis, the pathological process and the mechanism of MODS, experimentation to replicate an ideal animal model was mandatory. So porcine model of MODS was replicated in the first part of our study. Fifteen healthy male minipigs weighing 25.22士3.17Kg were randomly divided into two groups. One group was subjected to hemorrhagic shock plus endotoxiemia (group M, n=9). Another group was normal control only with anesthesia and sham operation (group C, n=6). Blood specimens were collected every 24 hours during the seven-day observation for the detection of serum SGPT, SGOT, Cr, BUN and gas analysis, which were used to judge if MODS occured by comparing with the initial value of itself. Histological changes of the main organs were observed under light microscope(LM). The mobidity and mortality of MODS in group M were 88.9% and 77.8% respectively, both much higher than group C. The two-hit model of MODS is based on the premise that an initial insult primes the host so that a subsequent activating event provokes an ex...
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