Splanchnic origin of cytokines in a porcine model of mesenteric ischemia-reperfusion

Background. The purpose of this study was to determine whether the gut or the liver was the source of tumor necrosis factor (TNF), interleukin-6 (IL-6), and endogenous endotoxin in a porcine model of mesenteric ischemia-reperfusion. Methods. Endotoxin, TNF, and IL-6 level were measured from the carotid artery (CA), portal vein (pv), and hepatic vein (HV) every 30 minutes for 330 minutes in anesthetized pigs after occlusion of the superior mesenteric artery (SMA; n = 7) and after sham operation (n = 7). In animal subjected to mesenteric ischemia, the SMA clamp was released twice: once at 240 minutes (for 40 seconds) and once at 300 minutes (for the remainder of the experiment). Results. In control animals, TNF and IL-6 levels remained at baseline at all vascular sites for the duration of the experiment. In the SIMA ligation group, TNF levels peaked before release of the SMA clamp. Compared with TNF levels in the CA (27 +/- 3.7 pU/ml, unchanged from baseline), TNF levels were higher in the PV and in the HV (47 +/- 1.7 and 44 +/- 4.0 pU/ml, respectively; p < 0.05). In contrast, IL-G appeared in the circulation immediately after first release of the SMA clamp. At this instant, compared with levels in the CA (1381 +/- 305 pU/ml), IL-6 levels in the PV and HV were higher (1884 +/- 276 and 1795 +/- 213 pU/ml, respectively; p < 0.05) Endotoxin remained at baseline levels (1.0 +/- 0.3 endotoxin unit/ml) throughout the experiment in both groups of animals, and gut efflux of endotoxin never exceeded gut influx. Conclusions. TNF is produced in a partially perfused splanchnic bed during SMA clamping (e.g., pancreas, duodenum, liver; left colon). IL-G is produced in gut during SMA clamping and is released when the SMA is unclamped. There is no apparent splanchnic release of endotoxin during or after SMA clamping in this model.