Ulinastatin ameliorates gastrointestinal injury sustained in a 2-hit porcine model of septic shock

Abstract

BackgroundUlinastatin is protective against organ dysfunction in severe disease. We investigated the extent of gastrointestinal tract injury and the potential protective effect of ulinastatin in a 2-hit porcine model of septic shock. MethodsPigs were randomized to 4 groups, 3 septic shock groups (12 per group)—vancomycin (VAN), vancomycin + ulinastatin (VAN + ULI), and saline (SAL)—and a sham-operated group (n = 10). Septic shock was induced by 2 hits: acute lung injury and Staphylococcus aureus challenge. Four hours after the 2 hits, pigs in septic shock received a central venous injection of vancomycin, vancomycin + ulinastatin, or saline. Hemodynamic status and blood samples were obtained. Serum d-lactate, diamine oxidase, and intestinal fatty acid–binding protein were determined, and gastrointestinal ATP enzyme activity was measured. Pathological and ultrastructural tests were performed. ResultsGastrointestinal tract injury after septic shock was significant. Compared with the SAL and VAN groups, the VAN + ULI group had better hemodynamic parameters (improved mean arterial pressure and cardiac output) (P< .05) and improved oxygen metabolism (oxygen delivery and consumption) (P< .05). In VAN + ULI group, serum d-lactate, diamine oxidase, and intestinal fatty acid–binding protein were significantly reduced (P< .05). Moreover, Na+-K+- and Ca2+-ATPase enzyme activity was significantly high (P< .05). Pathological and ultrastructural changes showed that severe gastrointestinal injury was significantly ameliorated in the VAN + ULI group vs the SAL and VAN groups. ConclusionsGastrointestinal injury and abnormal energy metabolism are remarkable following septic shock. Ulinastatin can improve energy metabolism and ameliorate injury to the gastrointestinal mucosa in the early stage of septic shock.