UC San Diego

Shock is one of the major challenges faced by modern medicine. Unless death occurs abruptly, it likely results from multiple organ failure following a shock-induced inflammatory cascade. While the precise events leading to multiple organ failure are still unclear, the intestine has been implicated as one of the key organs in ischemia- reperfusion induced injury. Due to the intestine's unique digestive function, pancreatic enzymes have been implicated to play a major role in the propagation of the inflammatory response. The objective of this study was to investigate enzymatic activity in selected non-ischemic secondary organs (liver, lung, brain, heart and kidney) following ischemia and reperfusion of the splanchnic circulation by occlusion of the superior mesentery and ciliac arteries. In order to determine the level of lipase and protease activity in these organs, in situ zymography was performed. For this technique, frozen sections of tissue were exposed to protease and lipase substrates. In the event of cleavage, the substrate became fluorescent and could be measured and analyzed quantitatively through digital microscopy and imaging techniques. The results of these measurements show that following splanchnic ischemia -reperfusion, protease activity is only upregulated in the intestine and pancreas, but remains unchanged in the liver, lung, brain, heart and kidney. In contrast, lipase activity was found to be unchanged in all of the organs investigated in this study (brain, heart, intestine, kidney, liver, lung, and pancreas). These results indicate that following splanchnic ischemia-reperfusion, changes in the enzymatic activity of secondary organs may not be critical to their subsequent failure. Rather, exogenous mediators possibly originating from the splanchnic circulation may be instrumental to the eventual failure of these organs in this shock model