Hypertonic saline resuscitation after mesenteric ischemia/reperfusion induces ileal apoptosis

Ernest A. Gonzalez, Rosemary A. Kozar, James W. Suliburk, Norman W. Weisbrodt, David W. Mercer, Frederick A. Moore

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: We have previously demonstrated that hypertonic saline (HS) resuscitation decreased inflammation and mucosal injury after mesenteric ischemia/ reperfusion (I/R). In contrast to I/R cell necrosis, apoptosis provides controlled cell death that minimizes inflammation. We therefore hypothesized that HS resuscitation after mesenteric I/R would induce apoptosis and decrease mucosal injury. Methods: Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then received no resuscitation or resuscitation with 4 mL/kg of HS, 4 mL/kg of lactated Ringer's (LR) solution (equal volume), or 32 mL/kg of LR solution (equal salt load). Rats were killed at 6 hours of reperfusion, and ileum was harvested for analysis. DNA fragmentation (apoptosis) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and mucosal injury by histology (Chiu score 0-5). Caspase-3 (proapoptotic mediator) and Bcl-xL (antiapoptotic mediator) protein expression were analyzed by Western immunoblot. Results: SMAO with no resuscitation, SMAO with 4 mL/kg of LR, and SMAO with 32 mL/kg of LR increased apoptosis (quantitated by TUNEL) and I/R-induced mucosal injury (quantitated by Chiu score). This was associated with an increase to similar levels in both proapoptotic caspase-3 and antiapoptotic Bcl-xL protein expression. Moreover, SMAO with 4 mL/kg of HS further increased apoptosis but decreased mucosal injury. This was associated with a differential expression of proapoptotic caspase-3 over antiapoptotic Bcl-xL. Conclusion: HS resuscitation after mesenteric I/R significantly increased ileal mucosal apoptosis while decreasing mucosal injury and may represent a novel mechanism by which HS resuscitation after mesenteric I/R reduces inflammation and imparts protection to the gut.

Original languageEnglish (US)
Pages (from-to)1092-1098
Number of pages7
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume59
Issue number5
DOIs
StatePublished - Nov 2005

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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