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Splanchnic production of cytokines in porcine models of septic shock and mesenteric ischemia-reperfusion

University of British Columbia

Multiple organ dysfunction syndrome (MODS) is a lethal sequela of septic shock and may occur in association with intestinal ischemia and/or reperfusion. Its pathogenesis may be mediated by endogenous endotoxin and cytokines. It is postulated that, during septic shock and intestinal ischemia, translocation of endotoxin from the gut lumen to the portal circulation occurs and the gut and the liver are major sources of cytokines. Two experiments were performed to test these hypotheses. In the first experiment, differences in fluxes of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) across the gut and liver were determined over 4 h in animals given endotoxin (50 p-g/kg; N=6) and in control animals (N=6). At no time did gut efflux of cytokines or endotoxin exceed gut influx of these substances, in either control or septic animals. Moreover, at no time did hepatic influx and efflux of TNF and IL-6 differ in either group. Therefore, net gut production of LPS, TNF or IL-6 in this porcine model of septic shock was not demonstrated. Further, net production of TNF or IL-6 by the liver was not observed. In the second experiment, endotoxin, TNF and IL-6 levels were measured from the carotid artery, portal vein and hepatic vein every 30 minutes over 330 min in pigs, following occlusion of the superior mesenteric artery (SMA; N = 7) and following sham surgery (N = 7). In animals subjected to mesenteric ischemia, the SMA clamp was released twice: once at 240 min (for a duration of 40 s), and once at 300 min (for the remainder of the experiment). Gut efflux of TNF and IL-6 did not exceed gut influx, and hepatic influx of T N F and IL-6 was the same as hepatic efflux in both groups throughout the experiment. The temporal relationships of the appearances of TNF and IL-6 at the various vascular sites suggested TNF is produced in a partially perfused splanchnic bed (eg: pancreas, duodenum, liver, left colon) and IL-6 is produced in ischemic gut. There was no apparent splanchnic release of endotoxin secondary to mesenteric ischemia-reperfusion.

Thesis/Dissertation

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2009-02-12

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http://hdl.handle.net/2429/4519

Surgery

University of British Columbia

UBCV

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