Gut gavage with antiendotoxin antibodies reduces the liberation of tumor necrosis factor-alpha after hemorrhage/resuscitation

OBJECTIVE: To evaluate the effect of gut gavage both alone and with enteral administration of monoclonal antibodies to endotoxin on the liberation of tumor necrosis factor (TNF)-alpha and subsequent hemodynamics after hemorrhage/resuscitation. DESIGN: Dose response intervention, sham-controlled animal study. SETTING: Research laboratory at a university medical center. ANIMALS: Instrumented rats (250-325 g body weight) underwent standardized hemorrhage/resuscitation. INTERVENTIONS: Animal groups received 4 hrs before hemorrhage/resuscitation: gastric gavage with Colyte alone (group 1), combined with E5 antiendotoxin at either 0.2 mg/100 g (group 2) or 2 mg/100 g body weight (group 3), or sham controls (group 4). There were six animals studied in each of the four groups. MEASUREMENTS AND MAIN RESULTS: For animals receiving gut gavage and high-dose E5 antiendotoxin, plasma concentrations of TNF-alpha (pg/mL) at 120 mins after hemorrhage/resuscitation were significantly lower compared with sham controls (16+/-4 group 3; 65+/-36 group 4; mean +/- SD, p < .05). At 300 mins, this same treatment group had a significantly higher mean blood pressure (mm Hg) (110+/-6 group 3; 86+/-7 group 4: p < .05). Also at 300 mins after hemorrhage/resuscitation, plasma lactate concentrations (mmol/L) were significantly lower for all gut gavage treatment groups compared with sham control animals (1.9+/-0.2 group 1; 2.0+/-0.2 group 2; 1.8+/-0.2 group 3; 4.8+/-2.8 group 4, p < .05). CONCLUSIONS: Prior treatment with gut gavage and enterally administered antiendotoxin antibodies reduces TNF-alpha liberation after hemorrhage/resuscitation and confers a subsequent improvement in hemodynamics and decreased plasma lactate concentrations. Such therapy may be efficacious in patients undergoing elective procedures where major hemorrhage is likely or in severely injured patients with continued or recurrent hemorrhage.