CHARACTERIZATION OF HYPOTHERMIC INTESTINAL ISCHEMIA-REPERFUSION INJURY IN DOGS - EFFECTS OF GLYCINE

The effects of 48 hr of hypothermic (4 degrees C) ischemia and short-t erm reperfusion (I-R) on intestinal function and metabolism were studi ed in dogs utilizing Collins flush alone or with the putative cytoprot ectant amino acid, glycine. Intestinal blood flow after hypothermic is chemia in Collins-flushed segments briefly rose at reperfusion, rapidl y declined after 5 min, and plateaued over the 60-minute reperfusion p eriod. Paired intestinal segments flushed with 5 mM glycine demonstrat ed parallel changes in blood flow over the reperfusion period, but the blood flow values were significantly higher (100-300%), relative to t he Collins segments. Intestinal oxygen consumption (VO2) was about 50% of normal nonischemic intestinal segments at all times after reperfus ion. The glycine-flushed intestinal segments significantly consumed ab out 100% more oxygen, relative to the paired control intestines. Intes tinal fluid and protein flux into the lumen significantly increased af ter I-R in both glycine- and Collins-flushed segments. Mucosal tissue myeloperoxidase (MPO) activity, a biochemical marker of neutrophils, s ignificantly increased after 48 hr of cold ischemia with Collins flush and 1 hr of reperfusion, relative to tissue obtained before ischemia. The reperfusion-induced increase in MPO activity was abolished in int estinal segments flushed with glycine. Mucosal synthesis of the chemoa ttractant leukotriene B-4 (LTB(4)) significantly increased after I-R a nd glycine flush abolished these increases. Nitric oxide synthesis by mucosal tissue in Collins-flushed segments subjected to 48 hr of hypot hermic ischemia and 1 hr of reperfusion was significantly higher, comp ared with nonischemic tissue or mucosal tissue subjected to cold ische mia without reperfusion. Glycine flush did not alter this pattern of N O synthesis. Light microscopic analysis in both Collins- and glycine-f lushed segments revealed that intestinal hypothermic ischemia and repe rfusion caused significant morphologic changes characterized by loss o f villus epithelium, decreased villus height, and venous congestion. T hese data indicate that glycine significantly improved oxygenation aft er hypothermic ischemia and reperfusion and prevented the I-R-induced increase in tissue neutrophil infiltration and leukotriene synthesis.