OBJECTIVE: To evaluate the effects of gut decontamination on endotoxin, tumor necrosis factor (TNF) levels, and the associated lung injury in a rat model of bowel ischemia. SUMMARY BACKGROUND DATA: Gut ischemia induces disruption of the intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into the blood, which may trigger a systemic inflammatory response and lung injury. METHODS: Thirty anesthetized rats were randomized into three groups: (1) ischemia-reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of reperfusion, n=10); (2) rats that underwent gut decontamination prior to ischemia (I/R+GD, n=10); and (3) control rats (sham operated, n=10). Serum levels of lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. RESULTS: One hour of bowel ischemia and 4 h of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33+/-0.005 EU/mL and 173+/-56 pg/mL, which were higher than the sham group (p<0.01). Gut decontamination (I/R+GD) significantly attenuated the LPS and TNF generation, 0.09+/-0.005 and 56.2+/-6 pg/mL (p<0.01). Lung injury as assessed by pulmonary permeability index was also reduced by gut decontamination, 2.1+/-0.42 vs 5.3+/-0.82 in the control group (p<0.03). Surprisingly no difference was detected in the number of pulmonary neutrophils in sequestration between the groups. CONCLUSIONS: Our data suggest that gut decontamination can reduce the generation of LPS, TNF, and the severity of lung damage that often follows ischemia and reperfusion of the intestine in rats.
OBJECTIVE: To evaluate the effects of gut decontamination on endotoxin, tumor necrosis factor (TNF) levels, and the associated lung injury in a rat model of bowel ischemia. SUMMARY BACKGROUND DATA: Gut ischemia induces disruption of the intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into the blood, which may trigger a systemic inflammatory response and lung injury. METHODS: Thirty anesthetized rats were randomized into three groups: (1) ischemia-reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of reperfusion, n=10); (2) rats that underwent gut decontamination prior to ischemia (I/R+GD, n=10); and (3) control rats (sham operated, n=10). Serum levels of lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. RESULTS: One hour of bowel ischemia and 4 h of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33+/-0.005 EU/mL and 173+/-56 pg/mL, which were higher than the sham group (p<0.01). Gut decontamination (I/R+GD) significantly attenuated the LPS and TNF generation, 0.09+/-0.005 and 56.2+/-6 pg/mL (p<0.01). Lung injury as assessed by pulmonary permeability index was also reduced by gut decontamination, 2.1+/-0.42 vs 5.3+/-0.82 in the control group (p<0.03). Surprisingly no difference was detected in the number of pulmonary neutrophils in sequestration between the groups. CONCLUSIONS: Our data suggest that gut decontamination can reduce the generation of LPS, TNF, and the severity of lung damage that often follows ischemia and reperfusion of the intestine in rats.
Authors: Ross F Goldberg; William G Austen; Xiaobo Zhang; Gitonga Munene; Golam Mostafa; Shaluk Biswas; Michael McCormack; Kyle R Eberlin; John T Nguyen; Hamit S Tatlidede; H Shaw Warren; Sonoko Narisawa; Jose L Millán; Richard A Hodin Journal: Proc Natl Acad Sci U S A Date: 2008-02-21 Impact factor: 11.205