ISCHEMIA REPERFUSION INJURY IN THE RAT COLON

This study investigated metabolic and biochemical consequences of colo nic ischemia/reperfusion (I/R) in the rat and evaluated whether antiox idants prevent I/R-induced functional damage in the rat colon. The sur gical preparation involved a 10 cm segment of the colon and occlusion of the superior mesenteric artery (SMA) to induce I/R. Arterial blood from the aorta and venous blood from the superior mesenteric vein (SMV ) was collected to measure blood gases, lactic acid (LA) and arachidon ic acid (AA) metabolites. Tissue xanthine oxidase (XO) and thiobarbitu ric acid (TEA) derivatives were measured before and after reperfusion. In addition, vascular and mucosal permeability, and the effect of MDL 73404 (a water soluble vitamin E analog) and 5-aminosalicylic acid on LA, AA, XO and TEA was measured. After ischemia, the colon displayed a metabolic shift from aerobic to anaerobic course by increasing lacti c acid production in the colon (183% increase in SMV lactate level com pared 87% in the SMA; p < 0.03). After 10 minutes of reperfusion, circ ulating 6-keto-prostaglandin F-1 alpha increased by 3.85 fold (p < 0.0 01) and thromboxane B-2 increased by 2 to 3 fold. An Ischemia time lon ger than 60 minutes was required to cause changes in tissue XO levels. Tissue TEA levels showed a good dose response corresponding with I/R time. I/R (60 minutes) caused a three and 16 fold increase (p < 0.01) in vascular and mucosal permeability, respectively. MDL 73404 and 5-am inosalicylic acid significantly inhibited the vascular permeability an d decreased LA, AA, XO and TEA. These observations provide the first d irect experimental evidence for I/R-induced damage in the colon and so me of its effects can be reversed by conventional and novel antioxidan ts.