FRUCTOSE 1-6 DIPHOSPHATE PREVENTS INTESTINAL ISCHEMIC REPERFUSION INJURY AND DEATH IN RATS

This study of ischemic and postischemic reperfusion intestinal injury in rats evaluates the potential therapeutic value of fructose 1-6 diphosphate on the basis of its ability to enhance anaerobic carbohydrate metabolism during ischemia and to prevent additional tissue injury after reestablishing blood flow by inhibiting the neutrophils to produce oxygen free radicals. In pursuit of this goal, 28 rats were randomized into 4 groups: pretreated with fructose 1-6 diphosphate (n = 7); pretreated with glucose (n = 7); postreperfusion treated with fructose 1-6 diphosphate (n = 7); and postreperfusion treated with saline (n = 7). Five additional rats were sham operated. Following 30 min occlusion of the superior mesenteric artery, all rats received their respective treatments for 5 days. Postreperfusion arterial pressure was significantly lower in the control rats (p < 0.001) as well as when compared with the fructose 1-6 diphosphate groups (p < 0.001). Significant increase in white blood cell counts occurred in the controls (p < 0.001), whereas in the fructose 1-6 diphosphate groups white blood cell counts were no different from preischemic values. All control rats that died in < 5 days had transmural intestinal necrosis, whereas in 3 of the controls that survived 5 days, partial intestinal necrosis was noted. Only one fructose 1-6 diphosphate-treated rat had partial intestinal necrosis. The overall 5-day survival was 100% for shamoperated rats, 93% for fructose 1-6 diphosphatetreated rats, and 21% for controls (fructose 1-6 diphosphate vs. controls, p < 0.001; fructose 1-6 diphosphate vs. sham, NS). The results are discussed and explained in terms of the postulated mechanism based on the pharmacological properties of fructose 1-6 diphosphate. © 1990.