ARACHIDONIC-ACID METABOLISM IN INTESTINAL HYPOTHERMIC PRESERVATION INJURY

The effect of hypothermic intestinal ischemia and short-term reperfusi on on mucosal arachidonic acid metabolism was studied in a dog model o f intestinal presentation injury. Canine intestinal segments were Rush ed with cold Collins solution, cold stored (4 degrees C) for either 24 or 48 h, and subsequently reperfused in the donor for 1 h. Samples of intestinal mucosa obtained before ischemia, after the ischemia period , and after the reperfusion period were placed into tissue culture. an d arachidonic acid metabolites were measured in the tissue incubation media. Prostaglandin E(2) (PGE(2)) and prostacyclin (PGI(2)) productio n significantly increased after 2 1 h of cold ischemia and after 1 h o f reperfusion, respectively. Intestines cold stored for 48 h and after 1 h of reperfusion produced significantly elevated quantities of thro mboxane B-2, PGI(2), PGE(2), and leukotriene B-4, relative to the prod uction rates from nonischemic control tissue or tissue subjected to 48 h of hypothermic ischemia without reperfusion. Mucosal production of thiol ether leukotrienes (LTC(4), LTD(4), LTE(4)) was not altered by i schemia or reperfusion at any time of cold ischemia. The synthesis of the lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE) was nor altered by hypothermic ischemia or reperfusion, but this arachido nate metabolite was produced by small intestinal mucosa in the greates t quantities. Specifically, nanogram quantities of 12-HETE were produc ed by intestinal mucosa compared to picogram quantities of the other m etabolites measured. Significant synthesis of the delta lactone deriva tive of 5-hydroxyeicosatetraenoic acid was detected by HPLC in many ti ssue samples undergoing 48 h of ischemia and reperfusion, relative to nonischemic tissue samples. In conclusion, significant increases in ar achidonate cyclooxygenase and lipoxygenase metabolites have been ident ified in intestinal mucosa subjected to long-term hypothermic ischemia and short-term reperfusion. Synthesis of these products increases wit h the duration of cold ischemia and may play a role in intestinal pres ervation injury. (C) 1996 Academic Press, Inc.