Cyclooxygenase-2 (COX-2) plays a role in mediating impaired intestinal transit after gut ischemia/reperfusion (I/R)

Abstract

Introduction: We have shown that gut I/R impairs intestinal transit. Schwartz et al have shown that COX-2 mediates impaired transit after bowel manipulation (Gastroenterology121:1354, 2001). We, therefore, hypothesized that COX-2 inhibition would abrogate impaired transit after gut I/R. Methods: Rats were pretreated with NS-398 (COX-2 inhibitor) 30 mg/kg IP or vehicle 1 hr prior to 60 min superior mesenteric artery occlusion (SMAO) or sham laparotomy. After 6 hrs reperfusion, transit was determined by quantitating % tracer in 10 segments of small intestine 30 min after injection into the duodenum (expressed as mean geometric center). Ileum was harvested for measurement of COX-1 and COX-2 mRNA by RT-PCR and PGE2 and 6-keto PGF1α levels by ELISA at 2 and 6 hrs reperfusion. Data are expressed as mean ± SEM, ANOVA (n = 6/group). Means with different superscripts are significantly different. Significance equals p < 0.05. Results: COX-1 mRNA did not increase at 2 hr (0.0 9 ± 0.03) or 6 hrs (0.09 ± 0.03) compared to sham (0.14 ± 0.04). COX-2 mRNA was significantly increased at 2 hr (0.47 ± 0.06), but not at 6 hrs (0.18 ± 0.08) compared to sham (0.04 ± 0.01). PGE2 levels were significantly elevated at 2 hr (19,625 ± 5,150 pg/mg protein), but not at 6 hrs (2,760 ± 715) compared to sham (5,337 ± 1,480). Similarly, 6-keto PGF1α levels were significantly elevated at 2 hrs (17,360 ± 2,201) pg/mg protein), but not at 6 hrs (5,013 ± 822) compared to sham (5,947 ± 2,522). NS-398 did not effect transit in sham, but significantly improved transit after SMAO (Fig). Conclusion: COX-2 plays a role in mediating impaired intestinal transit after gut I/R.