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August 1994

Effects of a Novel 21-Aminosteroid or Methylprednisolone in Experimental Total Intestinal Ischemia

Arch Surg. 1994;129(8):857-860. doi:10.1001/archsurg.1994.01420320083016

Objective:  To investigate whether tirilazad mesylate, a 21-aminosteroid, protects the small intestinal mucosa from injury following total warm or cold ischemia and reperfusion.

Design:  Randomized vehicle-controlled experimental study.

Setting:  A university department of surgery.

Animals:  Wistar rats. The warm ischemia series preceded the cold ischemia series. Animals were randomized within each series. Microscopic evaluation was performed on coded tissue slides.

Interventions:  Warm ischemia was induced by a hydrostatic pressure cuff inflated to 10 mm Hg above the systolic arterial pressure for 60 minutes. Cold ischemia was studied after small intestinal transplantation. The transplant was stored for 5 hours in University of Wisconsin solution at 8°C. Ischemia was followed by 60 minutes of reperfusion. In both series, tirilazad mesylate (3 mg/kg) or methylprednisolone sodium succinate (30 mg/kg) was given. Controls were given tirilazad vehicle or saline solution.

Main Outcome Measure:  Microscopic grade of small intestinal mucosal injury.

Results:  Mucosal injury was evident in all groups of animals that were subjected to warm or cold ischemia. Reperfusion following cold ischemia induced a significant reperfusion injury. Neither tirilazad nor methylprednisolone protected the small intestinal mucosa during ischemia or reperfusion.

Conclusion:  Mucosal injury following warm or cold intestinal ischemia and reperfusion is caused by factors other than or in addition to lipid peroxidation, which is preventable by use of a 21-aminosteroid.(Arch Surg. 1994;129:857-860)