Hypertonic saline resuscitation after mesenteric ischemia/reperfusion induces ileal apoptosis

J Trauma. 2005 Nov;59(5):1092-8. doi: 10.1097/01.ta.0000188935.66504.00.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Caspase 3
  • Caspases / metabolism
  • Ileum / physiopathology
  • In Situ Nick-End Labeling
  • Intestinal Mucosa / physiopathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / therapy*
  • Saline Solution, Hypertonic / therapeutic use


  • Saline Solution, Hypertonic
  • Casp3 protein, rat
  • Caspase 3
  • Caspases