Application of prostaglandin E2 improves ileal blood flow in NEC.

PURPOSE: Indomethacin, a nonselective prostaglandin inhibitor used to treat patent ductus arteriosus, is associated with intestinal perforation inducing an NEC-like illness. We sought to define the contribution of prostaglandin E2 (PG E2) and its receptor EP4 to intestinal blood flow regulation in premature neonates with NEC.

METHODS

Newborn Sprague-Dawley rats were randomized by litter to undergo experimental NEC induction or to serve as a CONTROL. At 48hours of age, intestinal laser Doppler blood flow was assessed at baseline and after intraperitoneal administration of indomethacin, PG E2, EP4 antagonist, or EP4 agonist. Data were analyzed using a 2-way ANOVA with post hoc Tukey-Kramer correction.

RESULTS

At baseline, NEC animals had lower intestinal blood flow than controls. Indomethacin, PG E2 and EP4 agonist all increased ileal blood flow, but PG E2 and EP4 agonist increased blood flow the most in NEC pups. EP4 antagonist decreased intestinal perfusion in both groups.

CONCLUSION

The above evidence suggests the importance of PG E2 and EP4 in regulation of neonatal intestinal blood flow. Since indomethacin treatment of patent ductus arteriosus in the premature infant is associated with an increased risk of intestinal perforation owing to compromised blood flow, PG E2 supplementation might provide intestinal protection if administered simultaneously with indomethacin.