M. A. Eid1, P. J. Matheson1,2, V. S. Graham1, 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: Potential complications of hemorrhagic shock (HS) include gut and liver hypoperfusion, splanchnic hypoxia, gut cytokine storm, acute lung injury (ALI), and/or acute respiratory distress syndrome (ARDS). While ALI/ARDS pathophysiology is multifactorial, lung polymorphonuclear neutrophil (PMN) infiltration occurs early in the cascade via increased intracellular adhesion molecule-1 (ICAM-1). We hypothesized that DPR treatment improves gut and liver perfusion to prevent these sequelae to decreased ALI/ARDS, and might mitigate ALI/ARDS following HS/CR.
Methods: Anesthetized male Sprague-Dawley rats (225-250g) were randomized to groups (n=8/group): 1) Sham, 2) HS/CR, 3) HS/CR+DPR (0), or 4) HS/CR+DPR (120). HS was 40% of baseline MAP for 60 minutes. CR was shed blood plus two volumes of normal saline over 30 minutes. DPR was intraperitoneal injection of 30mL pre-warmed 2.5% dextrose peritoneal dialysis solution. Serum and tissue were collected at 4 hours post-CR. Lung ICAM-1 ELISA and MPO activity assay were performed. Lung H&E and IHC for ICAM-1, VCAM-1, and MPO were blindly graded.
Results: HS/CR increased ICAM-1 levels and MPO activity compared to Sham, while DPR diminished these effects (see Table). In HS/CR, ICAM-1, VCAM-1, and MPO IHC staining increased compared to Sham, which was decreased with DPR. MPO IHC revealed increased PMN extravasation and increased absolute number per high-powered field in HS/CR groups compared to Sham, which both decreased below HS/CR levels with DPR.
Conclusion: Lung ICAM-1, VCAM-1, and MPO expression following hemorrhagic shock are modulated by peritoneal resuscitation using hypertonic peritoneal dialysis solution. These data suggest that resuscitation applied to the peritoneal space has a remote effect on lung pathophysiology associated with hemorrhagic shock. This study supports the finding of resuscitation with DPR in prior human trauma patient studies.
