Arachidonic acid metabolism in intestinal hypothermic preservation injury

The effect of hypothermic intestinal ischemia and short-term reperfusion on mucosal arachidonic acid metabolism was studied in a dog model of intestinal preservation injury. Canine intestinal segments were flushed 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, and arachidonic acid metabolites were measured in the tissue incubation media. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) production significantly increased after 24 h of cold ischemia and after 1 h of reperfusion, respectively. Intestines cold stored for 48 h and after 1 h of reperfusion produced significantly elevated quantities of thromboxane B2, PGI2, PGE2, and leukotriene B4, relative to the production rates from nonischemic control tissue or tissue subjected to 48 h of hypothermic ischemia without reperfusion. Mucosal production of thiol ether leukotrienes (LTC4, LTD4, LTE4) was not altered by ischemia or reperfusion at any time of cold ischemia. The synthesis of the lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE) was not altered by hypothermic ischemia or reperfusion, but this arachidonate metabolite was produced by small intestinal mucosa in the greatest quantities. Specifically, nanogram quantities of 12-HETE were produced by intestinal mucosa compared to picogram quantities of the other metabolites measured. Significant synthesis of the delta lactone derivative of 5-hydroxyeicosatetraenoic acid was detected by HPLC in many tissue samples undergoing 48 h of ischemia and reperfusion, relative to nonischemic tissue samples. In conclusion, significant increases in arachidonate cyclooxygenase and lipoxygenase metabolites have been identified in intestinal mucosa subjected to long-term hypothermic ischemia and short-term reperfusion. Synthesis of these products increases with the duration of cold ischemia and may play a role in intestinal preservation injury.