To investigate whether tirilazad mesylate, a 21-aminosteroid, protects the small intestinal mucosa from injury following total warm or cold ischemia and reperfusion.
Randomized vehicle-controlled ...experimental study.
A university department of surgery.
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.
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.
Microscopic grade of small intestinal mucosal injury.
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.
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.
We tested the hypothesis that circulating polymorphonuclear leukocytes (PMNs), adhering to endothelium of the liver vascular bed are involved in the alterations of the liver oxygen delivery (DO2) and ...consumption (VO2) that is a result of fecal peritonitis in pigs. Twenty-two pigs were divided into three groups. Animals in group I (n = 7) served as controls. Fecal peritonitis was induced in groups II (n = 7) and III (n = 8). Animals in group III were pretreated with IB4, a monoclonal anti-CD18 antibody inhibiting adherence of PMNs to the endothelium. Peritonitis increased liver VO2 in groups II and III in spite of decreased liver DO2. In group I, circulating PMNs increased during the experimental period. Sepsis caused a decrease in the number of circulating PMNs in group II, an effect that was fully counteracted in group III, where the number of PMNs rose to control level. Myeloperoxidase activity and morphometric determination of PMN infiltration in liver biopsies virtually paralleled the circulating PMN count. Although fecal peritonitis is followed by a CD18-dependent leukopenia that can be counteracted by pretreatment with an anti-CD18 antibodies, this treatment does not affect the alteration in liver VO2 and DO2 observed.
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