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.