Ketamine and the myenteric plexus in intestinal ischemia/reperfusion injury

Dig Dis Sci. 2010 Jul;55(7):1878-85. doi: 10.1007/s10620-009-0976-0. Epub 2009 Sep 16.

Abstract

Background and aims: Intestinal ischemia/reperfusion (I/R) is a common clinical entity with severe consequences. We studied the effects of ketamine and the participation of the myenteric plexus in I/R injury.

Methods: Rats were divided into six groups: sham, IR (30 min ischemia/60 min reperfusion), KET+IR (50 mg/kg i.p. ketamine injection before I/R), DEN (myenteric plexus ablated with benzalkonium chloride (BAC) and sham operation performed), DEN+IR (BAC treated and I/R induced), and DEN+KET+IR (BAC treated, ketamine administered, and I/R induced). Serum concentrations of p-selectin, intracellular adhesion molecule-1 (ICAM-1), and antithrombin III (ATIII) were measured, and tissue samples were obtained for histological analysis.

Results: IR group had higher intestinal mucosa injury and elevated serum concentrations of ICAM-1 and p-selectin, as well as ATIII depletion, compared with sham group (P < 0.05). In KET+IR group these alterations were significantly reduced (P < 0.05). DEN group showed ICAM-1 elevations when compared with sham group (P < 0.05), and DEN+IR group showed no difference in any parameter compared with IR group. However, ketamine administration in group DEN+KET+IR had no effect on any parameter when compared with DEN+IR group.

Conclusions: Ketamine was able to diminish alterations induced by I/R. Myenteric plexus ablation with BAC treatment alone had no effects on intestinal I/R injury. However, this procedure abolished ketamine's protective effects. Ketamine seems to require an intact enteric nervous system to exert its protective action.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antithrombin III / metabolism
  • Benzalkonium Compounds / pharmacology*
  • Biomarkers / blood
  • Disease Models, Animal
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intestinal Mucosa / blood supply
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestines / blood supply*
  • Ischemic Preconditioning / methods
  • Ketamine / pharmacology*
  • Male
  • Myenteric Plexus / drug effects*
  • P-Selectin / blood
  • P-Selectin / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reference Values
  • Reperfusion Injury / blood
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Sensitivity and Specificity

Substances

  • Benzalkonium Compounds
  • Biomarkers
  • P-Selectin
  • Intercellular Adhesion Molecule-1
  • Ketamine
  • Antithrombin III