REPERFUSION INJURY AND LIPID ABSORPTION

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It has been demonstrated both clinically and experimentally that ischemia followed by reperfusion (I/R) is injurious to the gastrointestinal tract. However, most studies have focused either on the microvasculature or gross morphological changes in the mucosa. Changes in epithelial membrane permeability to macromolecules have also been used to assess mucosal damage, but this index provides little information regarding the functional integrity of the intestinal mucosa. Preliminary data indicate that intestinal lipid absorption is sensitive to I/R-induced injury and therefore it may be a useful functional index of intestinal mucosal integrity after I/R insult. We therefore hypothesize that: (1) I/R of the small bowel results in a reduction of its ability to absorb and transport a lipid test meal and the reduction is related to the duration of ischemia; (2) intestinal lipid absorption is a useful functional index of mucosal integrity; (3) restoration of normal intestinal lipid absorption is preceded by the proliferation of enterocytes and the subsequent replacement of injured cells by healthy enterocytes; and (4) ornithine decarboxylase is involved in the repair process. To test these hypotheses, we will perform the following experiments: Specific Aim 1: Establish and characterize our model by studying the effect of I/R on the digestion, absorption and lymphatic transport of a lipid test meal containing triglyceride and cholesterol. Specific Aim 2: Determine the extent of injury to the small intestine at various times following the I/R insult. Specific Aim 3: Assess the involvement of ornithine decarboxylase in the repair of the intestine injured by I/R. Specific Aim 4: Study the repair of the intestinal mucosa after I/R- induced injury. Specific Aim 5: Study the relationship between diet and the susceptibility of the small intestine to I/R-induced injury. The proposed studies will greatly enhance our understanding of the factors affecting I/R-induced injury and how the injury in turn affects the function of the small intestine. This study will also provide new and useful information regarding processes involved in the repair of the small intestine after I/R-induced injury. Thus the information provided by this study will not only be relevant to intestinal mucosal injury but also to intestinal transplants.