ENDOTOXEMIA AND REMOTE ORGAN INJURY FOLLOWING INTESTINAL REPERFUSION

This study addresses the hypothesis that endotoxin (LPS) is an importa nt proximal mediator of remote organ dysfunction following intestinal reperfusion. Sprague-Dawley rats underwent intestinal ischemia for 120 min followed by 60 min of reperfusion (IIR). Animals underwent pretre atment with polymyxin B (PMB, 200 mu g, sc) or the induction of tolera nce to LPS prior to assignment to the IIR or sham group. Controls rece ived equal volumes of normal saline. Lung and intestinal injury was qu antitated using an edema index. Bile flow was quantitated by measuring the volume of bile produced per 15 min. The intestinal edema index of IIR animals pretreated with PMB was nearly 50% less than that of sali ne-treated animals sustaining the same injury (P < 0.05). The inductio n of LPS tolerance reduced the edema index of IIR animals by 28% compa red to the saline-treated IIR group (P < 0.05). Neither treatment redu ced this parameter to that of sham-operated controls (P < 0.05). The l ung edema index of animals pretreated with PMB was 50% of that of sali ne-treated IIR animals (P < 0.05). This remained significantly greater than that of sham-operated controls (P < 0.05). LPS tolerance did not affect the lung edema index of animals sustaining IIR. Bile flow rate s following IIR were not significantly affected by PMB or LPS toleranc e. These data do not support the hypothesis that LPS is an important p roximal mediator of the remote organ injury associated with IIR. Howev er, they do suggest that LPS may be one of many mediators responsible for this injury. (C) 1994 Academic Press, Inc.