Inhibition of intestinal transit by resuscitation-induced gut edema is reversed by administration of L-NIL

Abstract

Background. Postresuscitation gut edema and associated gut dysfunction is a common and significant clinical problem seen after traumatic injury and shock. We have previously shown that gut edema without ischemia/reperfusion injury delays intestinal transit. We hypothesized that up regulation of iNOS protein plays a role in delayed intestinal transit associated with gut edema and is reversible by L-NIL. Methods. 1 hour prior to laparotomy, rats were pretreated with 10 mg/kg of L-NIL or vehicle and underwent 80 mL/kg of 0.9% saline + superior mesenteric vein partial occlusion (Edema) or sham surgery. A duodenal catheter was placed to evaluate intestinal transit using a fluorescent dye. At 6 h, the small bowel was divided and the mean geometric center (MGC) was calculated to express transit. Ileum was harvested for evaluation of iNOS protein expression by Western blotting and MPO activity. Tissue water was determined using the % wet-to-dry weight ratio to assess gut edema. Data are expressed as mean ± SEM, n = 3–6 and ∗ P < 0.05 using ANOVA. Results. Gut edema, expressed as increased tissue water, was associated with a decreased intestinal transit, elevated iNOS protein expression. Pretreatment with L-NIL improved intestinal transit and decreased expression of iNOS protein without decreasing intestinal tissue water compared to edema animals. There was no difference in the MPO activity among groups. Conclusion. Gut edema, in the absence of leukocyte infiltration, delays intestinal transit via an iNOS-mediated mechanism. TABLE—ABSTRACT P88 Tissue water (%Tissue Water) Intestinal transit (MGC) MPO activity (milliUnits) iNOS densitometry (arbitrary units) Sham 75 ± 1 4.6 ± 0.3 6 ± 2 0.6 ± 0.03 Edema 82 ± 2∗ 2.7 ± 0.3∗ 2 ± 0.4 1.2 ± 0.2 Edema + L-Nil 80 ± 1∗ 4.2 ± 0.6 4 ± 0.7 0.8 ± 0.03