Effects of a novel 21-aminosteroid or methylprednisolone in experimental total intestinal ischemia.

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 degrees 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.