M. A. Wilson1,2, P. J. Matheson1,2, J. L. Weaver1, C. D. Downard1,2, R. N. Garrison1,2, J. W. Smith1,2 1University Of Louisville,Department Of Surgery,Louisville, KY, USA 2Robley Rex Veterans Affairs Medical Center,Research,Louisville, KY, USA
Introduction: Hemorrhagic shock (HS), a significant cause of mortality in trauma patients, has traditionally been resuscitated with intravenous blood and fluid infusion (CR). While central hemodynamic variables can be restored with CR, vital organ blood flow can often drop causing intestinal hypoperfusion, hypoxia, gut inflammation, and remote organ dysfunction. The addition of Direct Peritoneal Resuscitation (DPR) can prevent intestinal and hepatic hypoperfusion and inflammation. We hypothesized that DPR would improve lung function in resuscitated HS (HS/CR) by altering levels of serum and lung inflammatory mediators (DAMPs).
Methods: Anesthetized Sprague-Dawley rats were randomly assigned to groups (n=8/group): 1) Sham (matching timeline but no HS, CR, or DPR) 2) HS/CR (HS=40% MAP for 60min, CR=shed blood + volumes NS); and 3) HS/CR+DPR. All groups were followed for 4hr post-RES. ELISA was used to measure serum and/or lung lipopolysaccharide (LPS), cytokines, hyaluronic acid (HA), high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), MYD88, TRIF. Statistics were by analysis of variance and Tukey-Kramer test a priori P value of 0.05.
Results: HS/CR increased serum levels of LPS, HA, pro-inflammatory cytokines (IL-1a, IL-1b, IL-6, and interferon-g), and HMGB1, and lung levels of TLR4 and MYD88 were increased but not TRIF compared to Shams. HS/CR+DPR decreased LPS, HA, cytokines, HMGB1, TLR4 and MYD88 levels but did not alter TRIF levels compared to HS/CR alone.
Conclusion: Gut-derived mediators of systemic inflammation can be modulated by peritoneal application of hypertonic DPR to prevent activation of lung inflammatory processes. DPR after hemorrhagic shock improved visceral blood flow, reduced tissue injury, reduced DAMP formation and serum levels of multiple inflammatory cytokines and chemokines. Direct peritoneal resuscitation has the potential to significantly improve morbidity and mortality by downregulating the systemic inflammatory response following hemorrhagic shock
