Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Abstract

Hurt RT, Matheson PJ, Smith JW, Zakaria ER, Shaheen SP, McClain CJ, Garrison RN. Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 303: G1144 -G1152, 2012. First published September 17, 2012 doi:10.1152/ajpgi.00278.2011.-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 ϭ 8/group): 1) sham (no HS); 2) HS (40% MAP/60 min) ϩ intravenous fluid conventional resuscitation [CR; shed blood ϩ 2 vol saline (SAL)/30 min]; 3) HSϩCRϩDPR (30 ml ip 2.5% glucose dialysate); or 4) HSϩCRϩSAL (30 ml ip saline). Histopathology showed lung and liver injury in HSϩCR and HSϩCRϩSAL 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 HSϩCR revealed organ edema formation that was prevented by adjunct DPR. HSϩCR and HSϩCRϩSAL had 34% mortality by 24-h post-RES, which was absent with DPR (0%). Liver IFN-␥ and IL-6 levels were elevated in CR compared with DPR or shams. TNF-␣ 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. hemorrhagic shock; liver blood flow; liver injury DESPITE ADVANCES IN TREATMENT and therapies, hemorrhagic shock (HS) remains a major cause of morbidity and mortality following trauma in the United States (18). The clinical role the liver plays during HS and in subsequent multiple organ failure (MOF) is unclear. The largest and most recent clinical study followed 1,962 trauma patients with injury severity score Ͼ 14 (ISS Ͼ14) during a 3-year period (17). Of the patients who met the study's inclusion criteria, 154 (7.9%) exhibited signs of liver dysfunction during their hospital course. In general, these patients with liver dysfunction were older and had higher injury severity scores and lower prehospital blood pressure (17). Patients who developed high serum levels of bilirubin, a serum marker of liver injury, had longer stays in the intensive care unit and higher mortality (16.2% vs. 2.5%) compared with patients with normal or slightly elevated bilirubin. While these observational...

Association Between MC-2 Peptide and Hepatic Perfusion and Liver Injury Following Resuscitated Hemorrhagic Shock

“…This experimental HS model is a relatively mild degree of HS, which, if left untreated for up to 24 hours, results in a 27% mortality rate. 5 We have not yet examined the mortality rate associated with the HS/CR+MC-2 group at 24 hours post-resuscitation. Our experimental model does not perfectly match currently proscribed clinical resuscitation regimens that include, for example, intravenous hypertonic saline, intravenous colloid, blood or blood product resuscitation, artificial blood products, direct peritoneal resuscitation, heparan sulfate, or hypothermia.…”

“…All samples were evaluated by pathologists blinded to experimental protocol and groups. 5,20 Liver was sectioned at 3 to 4 μm and graded as 0 (no or minimal injury); 1 (focal necrosis); 2 (centrilobular necrosis [zone 3]); 3 (submassive necrosis [zone 2 and 3]); or 4 (massive necrosis). Samples were examined on low power and high power (original magnification ×400).…”

“…Each feature was assigned a score from 0 to 3 based on its absence (0) or presence to a mild (1), moderate (2), or severe (3) degree, and a total cumulative histology score was determined. 5 …”

“…This hemorrhagic shock model carries a mortality of 27% at 24 hours post-resuscitation. 5 MC-2 was given (50 mg/kg, intravenously [IV]) at the time of return of shed blood.…”

“…1–3 The roles of the gut and liver in the progression to multiple organ failure (MOF) are not clear. 4,5 Downmodulation of the systemic inflammatory process during resuscitation might be beneficial in the treatment of HS. 6,7 We examined the ability of a novel peptide, MC-2, to inhibit proinflammatory cytokines, prevent edema, and improve hepatic perfusion in an experimental model of resuscitated HS.…”