J. L. Weaver1, S. Matheson1, P. Matheson1, C. Downard1, R. N. Garrison1, J. Smith1 1University Of Louisville,Department Of Surgery,Louisville, KY, USA
Introduction: Hemorrhagic shock (HS) is a significant cause of morbidity and mortality in trauma patients. Treatment has traditionally been intravenous fluids and blood products to restore intravascular volume. However, studies have shown that even after blood pressure normalizes, the visceral organs remain ischemic. This can lead to organ dysfunction, failure, and death. This prolonged ischemia is thought to be due in part to the activation of an inflammatory cascade of cytokines. Direct peritoneal resuscitation (DPR) improves blood flow to the abdominal organs. In this study we examine the effect of DPR on the body’s inflammatory response to hypotensive shock.
Methods: Rats were randomly assigned to three groups (n=8/group): 1) sham (no HS); 2) HS plus conventional resuscitation (CR); or 3) HS+CR+DPR. Rats were hemorrhaged to 40% MAP and resuscitated with shed blood and two volumes of normal saline. Group 3 rats were given intraperitoneal injections of 30cc 2.5% peritoneal dialysis solution. Effective hepatic blood flow (EHBF) was measured using a steady state of galactose. Tissue was collected at 4 hours post-resuscitation. Serum cytokines were measured using the Luminex immunoassay or ELISA.
Results: Central hemodynamics were restored post-hemorrhage in both groups, but EHBF fell after resuscitation was complete. This was prevented by adding DPR. The DPR groups had lower serum levels of hyaluronic acid (HA) and high-mobility group box-1 protein (HMGB-1), which are markers of cellular injury, when compared to the CR group. HMGB-1 is usually sequestered in the cell’s nucleus and immunohistochemistry staining shows this is maintained in the DPR group, but the nucleus is disrupted and HMGB-1 migrated to the cytosol in the CR group. The DPR group showed lower levels of inflammatory cytokines such as IL-1a, IL-1B, IL-6 and INF-γ. Histologic sections of terminal ileum in the DPR rats also demonstrated better preservation of architecture with less edema and necrosis.
Conclusion: The addition of DPR after HS improved visceral blood flow, demonstrated by the EHBF data. This led to a preservation of cell structure, seen on histology and via a reduction in HA and HMGB-1, which are released in cell necrosis. HMGB-1 is normally stored in the nucleus during apoptosis to prevent inflammatory signaling. It was released to the cytosol in the CR group but not the DPR group, which further proves worse necrosis with CR. DPR also returned levels of inflammatory cytokines to near-normal when compared to the CR group. These findings suggest that DPR reduces the inflammatory response which contributes to multiple organ-system failure after hemorrhagic shock, and has the potential to improve outcomes in trauma patients.
