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KMID : 0374019920150010023
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Ewha Medical Journal
1992 Volume.15 No. 1 p.23 ~ p.32
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The Effect of Enteral Allopurinol Suspension on the Intestinal Mucosal Injury and Survival Rate in the Mesenteric Ischemia of White Rats
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Abstract
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The sequelae of ischemic injury to the intestine are potentially devastating to the patient. And it has also been implicated as playing a major role in the development of necrotizing enterocolitis, a major cause of morbidity and mortality in the
newborn.
Many studies have demonstrated that allopurinol can reduce reperfusion injury after ischemia. But they have limited clinical significance because the data in those studies were produced using parenteral allopurinol unavailable for use in patients
or
enteral allopurinol at high-doses that is not tolerated and has prohibitive side effects.
This study evaluated the protective effects of clinically used doses of enteral allopurinol in rats with intestinal ischemia. One-hundrd sixteen Sprague-Dawley rats(180~250g) received allopurinol(1mg/100g) suspensin water(experimental group0 or
tap
water(controls) for 1 week. Four rats(2 treated with allopurinol and 2 controls) were used to identify histologic finding of small bowel mucosa. Sixteen rats(each 8 of allopurinol-treated and control) were used to measure serum uric acid levels
to
document systemic effects of allopurinol. Ninty-six rats were subjected to superior mesenteric vessels occusion for 20. 30 of 40 min to produce ischemic injury to the intestine. Segmental small bowel resections were performed in 12 control rats
and
12
allopurinol-treated rats before and after reperfusion to identify histopathologic evidence of reperfusion injury. And the remaining seventy-two rats( 36 of allopurinol-treated and control) were observed for mortality(death within 7 days) after
reperfusion.
Serum uric acid was decreased from 3.70±1.62mg/dl in controls to 2.41±0.75mg/dl in allopurinol-treated group. Mucosal injury severity was not different significantly among the periods of mesenteric vascular occlusion. But after 30 min of
reperfusion.
Severity of mucosal injuryin controls was significantly aggrevated and in allopurinol-treated groups was not different from injury severity of ischemic period. The lethal time 50%(LT50) in controls was between 30 and 40 min of ischemia. There was
reduction in mortality after allopurinol pretreatment in the presently available form and dose with 20, 30 or 40 min of ischemia. And the reduction of mortality in allopurinol-treated groups was distinguishable with LT50 of ischemic period.
This study has demonstrated that protective effects of allopurinol to mucosal injury caused by mesenteric ischemia can be achieved with enteral doses that are not likely to cause intolerable side effects and agonizing stress with daily gastric
lavage
chronically.
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KEYWORD
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