Gut mucosal injury is attenuated by recombinant bactericidal/permeability-increasing protein in hind limb ischemia-reperfusion injury

Lower limb ischemia-reperfusion injury (IRI) is associated with increased g ut permeability to endotoxin, which not only directly damages enterocytes b ut also stimulates a systemic inflammatory response syndrome (SIRS), compou nding gut injury. Recombinant bactericidal/ permeability-increasing protein (rBPI(21)) is a novel anti-endotoxin therapy with proven benefit in sepsis . Its potential role in modulating remote gut injury in hind limb IRI was s tudied. Male Wistar rats were chosen for a prospective randomized control t rial (n = 10 per group). The control group and two groups undergoing 3 hr b ilateral hind limb ischemia with 2 hr reperfusion (I/R) were randomized to receive intravenously either control protein thaumatin at 2 mg/kg or rBPI(2 1) at 2 mg/kg, respectively. Quantitative morphometric assessment of the sm all bowel was used as a measure of gut injury and, using an ex vivo everted gut sac model, translocation of C-14-labeled polyethylene glycol (PEG) was used as a measure of gut permeability. Our results indicate that hind limb IRI is associated with remote gut mucosal injury and increased permeabilit y to macromolecules. rBPI(21) anti-endotoxin therapy modulates remote gut i njury associated with lower limb IRI in this model.