Development and characterization of a rat model of nonpenetrating liver trauma.

The aim of this study was to develop and characterize a rodent model of liver trauma suitable for preclinical evaluation of new treatments and diagnostic technologies. Liver trauma was created by dropping a steel cylinder through a plastic tube onto the abdomen of supine, anesthetized rats. Internal hemorrhage in the absence of liver trauma was simulated by instilling fresh blood into the peritoneum. Platelet counts were elevated significantly after liver trauma but not simulated hemorrhage. Liver trauma and simulated internal hemorrhage both increased blood levels of the factor growth-regulated oncogene-Kupffer cell. Transcription of plasminogen activator inhibitor 1, heat shock protein 70, and suppressor of cytokine syntheses 3 was increased 77-, 22-, and 27-fold, respectively, 2 h after liver trauma but was unaltered by simulated internal hemorrhage. Levels returned to pretrauma levels by 24 h after trauma. Transcript levels for hypoxia-inducible transcription factor 1alpha were increased 2.8-fold at 24 h but not 2 h after trauma and were not affected by simulated hemorrhage. Production of heat shock protein 70 and inducible nitric oxide synthase in liver was limited to a penumbra surrounding areas of necrosis associated with trauma. The rat model described produces lesions similar to those that occur in humans after blunt trauma.