S. C. Jones1, P. J. Matheson1,2, C. D. Downard1,2, J. C. Frimodig1, C. J. McClain1,2, R. N. Garrison1,2, J. W. Smith1,2 1University Of Louisville,Department Of Surgery,Louisville, KENTUCKY, USA 2Robley Rex VAMC,Department Of Surgery,Louisville, KENTUCKY, USA
Introduction: ~~Hemorrhagic shock (HS) in trauma patients can result in gut and liver hypoperfusion and a pro-inflammatory systemic condition, which often initiates acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS). The pathophysiology of ALI/ARDS is multifactorial, but can involve alarmins, activated immune cells, and inflammatory chemokines/cytokines. DPR improves intestinal and hepatic blood flow to prevent gut-associated inflammatory changes and thus might also prevent or mitigate ALI/ARDS. We hypothesized that soluble intracellular adhesion molecule-1 (sICAM-1), which is sloughed from endothelial cells in inflammatory conditions, might be elevated in resuscitated HS, and that DPR might prevent that event.
Methods: ~~Male Sprague-Dawley rats (225-250g) were anesthetized and randomized to groups (n=8/group): 1) Sham (no HS, no conventional resuscitation or CR); 2) HS/CR; or 3) HS/CR+DPR. HS was 40% of mean arterial pressure for 60 minutes. CR was shed blood plus two equal volumes of lactated Ringers over 30 minutes total. DPR was 25mL of pre-warmed 2.5% glucose peritoneal dialysis solution at the time of blood infusion. Serum and lung tissue were collected at 4 hours post-CR. Adhesion molecule levels were measured by ELISA: serum sICAM-1, lung integrin-alpha L (ITGAL or LFA-1), and lung integrin-alpha M (ITGAM or MAC-1).
Results:~~HS/CR increased sICAM-1 levels compared to Sham, and DPR increased sICAM-1 further compared to Sham or HS/CR (see Figure). There were no differences in lung LFA-1 or MAC-1 levels in HS/CR or HS/CR+DPR compared to Sham.
Conclusion:~~These data suggest that circulating levels of sICAM-1 are not mediated by gut blood flow and/or gut-associated inflammatory mediators in this model of resuscitated shock at this 4-hour post-CR time point. Other post-resuscitation time points might reveal a benefit to DPR, which has been shown to improve the number of lungs suitable for organ transplant in human organ donors compared to donors who did not receive DPR treatment.
