Mechanisms of endotoxin-induced intestinal injury in a hyperdynamic model of sepsis.
The goal of this study was to test the hypothesis that endotoxin-induced bacterial translocation is the result of a selective decrease in intestinal blood flow that causes an oxidant-mediated intestinal mucosal injury. To accomplish this goal, 116 instrumented rats receiving a nonlethal dose of endotoxin (5 mg/kg IP) or saline were studied. Organ blood flow and cardiac output were measured using the microsphere technique and intestinal permeability was measured both by the blood to luminal clearance of 51Cr-EDTA and by horseradish peroxidase. Cardiac output was higher in the endotoxin-treated group than in the saline group (76 +/- 12 versus 95 +/- 17 mL/min; p < 0.05). Although endotoxin induced a hyperdynamic state, blood flow to the distal ileum and cecum was selectively decreased by 35%-50% (p < 0.01), whereas blood flow to the rest of the intestine, spleen, pancreas, and liver was normal. Furthermore, blood flow to the ileal mucosa was decreased to a greater extent than to the remainder of the gut wall (p < 0.05). Small bowel permeability to 51Cr-EDTA was increased at sites of decreased blood flow (ileum) but not at sites of normal (jejunum) blood flow. Allopurinol, a competitive inhibitor of xanthine oxidase, ameliorated the endotoxin-induced decrease in ileal blood flow as well as the increase in ileal permeability. Thus these studies support the hypothesis that endotoxin-induced mucosal injury is the result of an ischemia reperfusion-mediated injury of the distal small intestine and cecum.
Department of Surgery, Louisiana State University Medical Center, Shreveport 71130-3932.
D
D
Xu
L
L
Qi
D
D
Guillory
N
N
Cruz
R
R
Berg
E A
EA
Deitch
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D010544:Peroxidases / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms
D004731:Endotoxins; D000493:Allopurinol; D010544:Peroxidases