High dose versus low dose enteral allopurinol for prophylaxis in mesenteric ischemia

Studies demonstrating protective effects of allopurinol in intestinal ischemia have been carried out using i.v. allopurinol (presently unavailable for human use) or enteral allopurinol at supra-normal doses and, therefore, have questionable clinical relevance. We evaluated the protective effects of clinically used doses of enteral allopurinol in rats with intestinal ischemia. One hundred nine male Sprague-Dawley rats (250-300 gm) received enteral allopurinol (5-30 mg/kg) or water daily for 1 week and were subjected to superior mesenteric artery occlusion for 20, 30, or 45 min. Mortality in water-fed controls after 20 min of mesenteric ischemia was 50%, but there was no mortality in rats pretreated with allopurinol (5, 10, and 20 mg/kg/day) in this group (P = 0.016). There was no reduction in mortality after allopurinol pretreatment at any dose in rats with 30 or 45 min of ischemia. We concluded that 1) prolonged intestinal ischemia causes lethal damage during the hypoperfusion phase that cannot be prevented by allopurinol pretreatment even at supra-normal doses, and 2) allopurinol at recommended enteral doses (5-10 mg/kg/day) can reduce morality from reperfusion injury when the phase of hypoperfusion is not, in itself, lethal. Allopurinol is effective in reducing reperfusion injury in the currently available enteral form in dose ranges that should not cause prohibitive side effects.