Lisofylline ameliorates intestinal and hepatic injury induced by hemorrhage and resuscitation in rats

Objective: We sought to determine whether treatment with lisofylline (LSF) preserves intestinal barrier function in rats subjected to hemorrhagic shock and resuscitation (HS/R). Setting: Research laboratory at a major university teaching hospital. Design: Rats were bled to a mean arterial pressure of 30 mm Hg and maintained at that pressure for 90 mins. One group (n = 8) was treated with LSF (bolus doses of 15 mg/kg at 45 and 89 min plus infusion at 10 mg·kg^-1·hr^-1), whereas another group (n = 8) received only the lactated Ringer's solution (LRS) vehicle. At 90 mins, the animals were resuscitated with shed blood and LRS (55 mL·kg^-1·hr^-1). Intestinal mucosal permeability was determined by measuring the mucosal-to-serosal clearance of fluorescein isothiocyanate dextran (molecular weight = 4 kDa) into everted gut sacs. Measurements and Main Results: Intestinal and hepatic blood flow (assessed by laser Doppler flowmetry) was greater in LSF- treated rats. Treatment with LSF ameliorated the development of histologic evidence of mucosal damage and hyperpermeability. Rats treated with LSF had lower plasma concentrations of the intracellular hepatic enzyme, aspartate aminotransferase. After 90 mins of resuscitation, concentrations of adenosine triphosphate in intestinal and hepatic tissue were greater in LSF-treated as compared with LRS-treated rats, but concentrations of the endogenous antioxidant, glutathione, in intestinal and hepatic tissue, although lower than in rats not subjected to HS/R, were similar in the two treatment groups. Conclusion: Treatment with LSF ameliorated HS/R-induced derangements in intestinal structure and function and hepatic injury, possibly by preserving microvascular perfusion and tissue adenosine triphosphate concentrations.