M. A. Eid2, P. J. Matheson1,2,3, C. D. Downard1,2, R. N. Garrison1,2,3, J. W. Smith2,3 1Robley Rex Veterans Affairs Medical Center,Louisville, KY, USA 2University Of Louisville,Surgery,Louisville, KY, USA 3University Of Louisville,Physiology & Biophysics,Louisville, KY, USA
Introduction: Acute Lung Injury (ALI) leading to Adult Respiratory Distress Syndrome (ARDS) is an early sign of multiple organ dysfunction (MOD) after hemorrhagic shock (HS). Gut-derived pro-inflammatory factors via mesenteric lymph initiate systemic inflammatory response (SIRS), possibly via lung toll-like receptor 4 (TLR4). Adjunct Direct Peritoneal Resuscitation (DPR) following HS mitigates the inflammatory response. Deficiencies in downstream pathways from TLR4 (i.e., MYD88 and TRIF) attenuate SIRS by an unknown mechanism. We hypothesized that DPR would improve lung function in resuscitated HS (HS/CR) by altering levels of TLR4 and 2nd messengers MYD88/TRIF.
Methods: Anesthetized Sprague-Dawley rats were randomly assigned to groups (n=8/group): 1) HS/CR (HS=40% MAP for 60min, CR=shed blood + volumes NS); 2) HS/CR+DPR at time of CR; 3) HS/CR+DPR(120) at 120min post-resuscitation (postRES); 4) Sham (no HS, no CR, no DPR); 5) Sham + DPR at CR; and 6) Sham+DPR(120). All groups were followed for 4hr postRES. ELISA was used to measure lung TLR4, MYD88, and TRIF as well as mesenteric lymph and serum LPS.
Results: HS/CR increased LPS and TLR4 and MYD88 expression in the lung compared to Shams but did not alter TRIF (see Figure). HS/CR+DPR decreased TLR4 and MYD88 levels but did not alter TRIF levels. Delayed addition of DPR (HS/CR +DPR(120)) had a similar effect.
Conclusions: Gut-derived mediators of systemic inflammation can be modulated by peritoneal resuscitation with hypertonic peritoneal dialysis solution to prevent activation of lung inflammatory processes. These benefits occur when DPR is given immediately at the time of conventional resuscitation or when DPR is delayed by 2 hours after the start of conventional resuscitation.
