title: Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock.
abstract: Conventional resuscitation (CR) from hemorrhagic shock (HS) results in gut and liver hypoperfusion, organ and cellular edema, and vital organ injury. Adjunct direct peritoneal resuscitation (DPR) with dialysate prevents gut vasoconstriction, hypoperfusion, and injury. We hypothesized that DPR might also improve hepatocellular edema, inflammation, and injury. Anesthetized male SD rats were assigned to groups (n = 8/group): 1) sham (no HS); 2) HS (40% MAP/60 min) + intravenous fluid conventional resuscitation [CR; shed blood + 2 vol saline (SAL)/30 min]; 3) HS+CR+DPR (30 ml ip 2.5% glucose dialysate); or 4) HS+CR+SAL (30 ml ip saline). Histopathology showed lung and liver injury in HS+CR and HS+CR+SAL up to 24-h postresuscitation (post-RES) that was not in shams and which was prevented by adjunct DPR. Wet-to-dry weight ratios in HS+CR revealed organ edema formation that was prevented by adjunct DPR. HS+CR and HS+CR+SAL had 34% mortality by 24-h post-RES, which was absent with DPR (0%). Liver IFN-γ and IL-6 levels were elevated in CR compared with DPR or shams. TNF-α mRNA was upregulated in CR/sham and DPR/sham. IL-17 was downregulated in DPR/sham. CXCL10 mRNA was upregulated in CR/sham but downregulated in DPR/sham. Despite restored central hemodynamic performance after CR of HS, liver blood flow was compromised up to 24 h post-RES, and the addition of DPR restores and maintains liver perfusion at 24-h post-RES. DPR prevented liver injury, histological damage, and edema formation compared with CR alone. DPR provided a mitigating anti-inflammatory dampening of the systemic inflammatory response. In all, these effects likely account for improved survivorship in the DPR-treated group.
authors.affiliation: Departments of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Hurt
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: Jason W
authors.initials: JW
authors.lastname: Smith
authors.forename: El Rasheid
authors.initials: el R
authors.lastname: Zakaria
authors.forename: Saad P
authors.initials: SP
authors.lastname: Shaheen
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.forename: R Neal
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D004487:Edema / Q000517:prevention & control; D005440:Fluid Therapy / Q000379:methods; D006505:Hepatitis / Q000517:prevention & control*; D008102:Liver Circulation; D008297:Male; D010530:Peritoneal Dialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000009:adverse effects / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*