Prevention of deleterious effects of reperfusion injury using one-week high-dose allopurinol

Allopurinol has been widely used to reduce the severity of the reperfusion injury. However, conflicting data have been reported regarding the dosage, the duration of the timing, and the administrative regimen of the drug. The aim of this study was, therefore, to evaluate the effects of short versus long periods of allopurinol pretreatment on the anastomotic healing of inte stines, directly after being subjected to ischemia-reperfusion (IR) stress. Furthermore, the effects of an allopurinol pretreatment on the survival ra te following IR stress, was also assessed. One hundred thirty-seven male Wi star rats with a median weight of 235 (range, 180-275) g used in the study. In group I (control group, N = 20) superior mesenteric artery (SMA) and co llateral vessels were isolated but not occluded. In group II, the profound IR group (PIR, N = 42), the SMA was occluded immediately distal to the aort a with collateral interruption using an atraumatic arterial clip for 30 min . In group III [two days of allopurinol (ALL) pretreatment group, 2ALL, N = 38], allopurinol (100 mg/kg body wt) was given intraperitoneally on a dail y basis for two days prior to the experiment. In group IV (seven days of al lopurinol pretreatment group, 7ALL, N = 37), the same pretreatment and the allopurinol schedule was performed for seven days before surgery. All anima ls underwent 3 cm of ileal resection and primary anastomosis, 10 cm proxima l to ileocecal valve. Within each group, animals were anesthetized either o n the third or seventh postoperative days. Abdominal wound healing, intraab dominal adhesions, anastomotic complications, anastomotic bursting pressure measurements, and bursting site were recorded as were the histopathologic evaluation. No rats in group I, 20 rats in group II, 18 rats in group III, and 7 rats in group IV died (P = 0.0003). Anastomotic dehiscence was found in one of 20 group I, in 11 of 22 in group II, in 9 of 20 in group III, and in 3 of 30 in group IV (P = 0.0003). On the third and seventh days, the me dian bursting pressures of the anastomosis were determined: 42 and 235 mm H g in group I, 17 and 105 mm in Hg in group II, 22 and 183 mm Hg in group II I, and 36 and 214 mm Hg in group IV (P < 0.0001). The burst occurred at the anastomoses in all animals tested on the third postoperative day, one in g roup I, six in group II, four in group III and one in group TV on the seven th postoperative day (P < 0.01). All deleterious effects of reperfusion inj ury on intestinal anastomosis healing, including survival rates and the his topathological parameters, were significantly prevented by seven days, but not two days, of high-dose allopurinol pretreatment.