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.


METHODS
Randomized vehicle-controlled experimental study.


METHODS
A university department of surgery.


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Park
P O
PO
Department of Surgery, University of Uppsala, Sweden.
Gerdin
B
B
Haglund
U
U
D000818:Animals; D005069:Evaluation Studies as Topic; D005260:Female; D016166:Free Radical Scavengers; D007413:Intestinal Mucosa / Q000187:drug effects*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D011281:Pregnatrienes / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013696:Temperature
D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad