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 hemorrh age/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 h emorrhage/resuscitation. Interventions: Animal groups received 4 hrs before hemorrhage/resuscitation : gastric gavage with Colyte alone (group 1), combined with E-5 antiendotox in at either 0.2 mg/100 g (group 2) or 2 mg/100 II body weight (group 3), o r sham controls (group 4). There were six animals studied in each of the fo ur groups. Measurements and Main Results:For animals receiving gut gavage and high-dos e E-5 antiendotoxin, plasma concentrations of TNF-alpha (pg/mL) at 120 m in s after hemorrhage/resuscitation were significantly lower compared with sha m controls (16 +/- 4 group 3; 65 +/- 36 group 4; mean +/- SD, p < .05). At 300 mine, this same treatment group had a significantly higher mean blood p ressure (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 wit h 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 ant iendotoxin antibodies reduces TNF-alpha liberation after hemorrhage/resusci tation and confers a subsequent improvement in hemodynamics and decreased p lasma lactate concentrations. Such therapy may be efficacious in patients u ndergoing elective procedures where major hemorrhage is likely or in severe ly injured patients with continued or recurrent hemorrhage.