Endotoxemia and remote organ injury following intestinal reperfusion.
This study addresses the hypothesis that endotoxin (LPS) is an important 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 pretreatment with polymyxin B (PMB, 200 micrograms, sc) or the induction of tolerance to LPS prior to assignment to the IIR or sham group. Controls received equal volumes of normal saline. Lung and intestinal injury was quantitated 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 saline-treated animals sustaining the same injury (P < 0.05). The induction of LPS tolerance reduced the edema index of IIR animals by 28% compared to the saline-treated IIR group (P < 0.05). Neither treatment reduced this parameter to that of sham-operated controls (P < 0.05). The lung edema index of animals pretreated with PMB was 50% of that of saline-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 rates following IIR were not significantly affected by PMB or LPS tolerance. These data do not support the hypothesis that LPS is an important proximal mediator of the remote organ injury associated with IIR. However, they do suggest that LPS may be one of many mediators responsible for this injury.
Department of Surgery, University of Texas Southwestern Medical School, Dallas 75235-9031.
R H
RH
Turnage
K S
KS
Guice
K T
KT
Oldham
D000818:Animals; D004361:Drug Tolerance; D004731:Endotoxins / Q000097:blood* / Q000494:pharmacology; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries; D008099:Liver / Q000187:drug effects / Q000293:injuries; D008168:Lung / Q000187:drug effects; D055370:Lung Injury; D008297:Male; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000628:therapy*
D004731:Endotoxins; D011112:Polymyxin B