Key result
In rats undergoing colonic anastomosis with ischaemic-reperfusion injury, high-dose allopurinol reduced anastomotic leaks (20% vs 40%) and improved mean bursting pressure (65.2 vs 41 mmHg).
Why the study?
Does high-dose allopurinol improve healing of colonic anastomosis exposed to ischaemic-reperfusion injury in rats?
RCT (n=45)
Randomized
No
Does high-dose allopurinol improve healing of colonic anastomosis exposed to ischaemic-reperfusion injury in rats?
Absolute Event Rate: 20% vs 40%
High-dose allopurinol partially mitigates the deleterious effects of ischaemia-reperfusion injury on colonic anastomotic healing in a rat model.
Hypothesis-generating for allopurinol in rat colonic anastomosis; requires human trials before any clinical consideration.
Background: Research on intestinal ischaemic-reperfusion injury is at fever pitch (related to laparoscopy-intestinal transplant-mesenteric vessels revascularization) and in the past couple of years it becomes clear that its pathogenesis is either hypoxic or cytotoxic and represents an utmost universal step in the impaired intestinal anastomosis. Aim: We try to figure out the pathogenesis of intestinal ischaemic-reperfusion, its impact on the intestinal wound healing from the clinical, physical, biochemical and histological aspects and the role of antioxidants in prevention of its deserve effects. Design: Randomized controlled study. Setting: Research Laboratory Mansoura University. Participants: animal study. Material & methods: Right colonic transection and anastomosis was performed in 45 rats which were divided into 3 groups: GI. The control one, GII rats following one hour ischaemia of right colon and terminal ileum, reperfusion of these tissues was achieved till sacrification and GIII rats together with ischaemic-reperfusion “allopurinol” high dose was administered in the preoperative and postoperative periods. All animals were sacrified on the 5th postoperative day. Main outcome measures: Clinical assessment of anastomotic, physical measurement of anastomosis bursting pressure, biochemical assessment (oxidant MDA-antioxidant GSH-Px) and histological assessment (Ileal injury score-anastomotic healing). Results: clinically 6 cases of anastomotic leak in GII and 3 in GIII with no cases in GI, physically mean anastomotic bursting pressure in mmmHg was 117 in GI, 41 in GII and 65.2 in GIII. Histologically: mean score of intestinal mucosal injury was 0.9 in GI and 4.3 in GII and 2.4 in GIII while the wound healing parameters in GIII were better than in GII. Biochemically: the mean MDA expressed as nanomol/mg and the mean GSH-Px expressed as unit/mg respectively were (5.4-126) in GI, (21.5-150) in GII and (11.2-165) in GIII. Conclusion: The cytotoxic free radicals generation is an utmost universal step in the development of intestinal mucosal injury which has a deleterious effect on the intestinal wound healing (clinical, physical, biochemical, and histological). Lastly although the antioxidants not totally reversing the ischaemic reperfusion effects, the antioxidants seem to improve the intestinal wound healing.
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El-Awady et al. (2003) conducted an RCT in Intestinal ischaemic-reperfusion injury (n=45). Allopurinol vs. Ischaemia-reperfusion alone was evaluated on Anastomotic leak. In rats undergoing colonic anastomosis with ischaemic-reperfusion injury, high-dose allopurinol reduced anastomotic leaks (20% vs 40%) and improved mean bursting pressure (65.2 vs 41 mmHg).
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