Effect of indomethacin on mesenteric circulation in mongrel dogs

Necrotizing enterocolitis has been attributed to the use of indomethacin (INDO) for medical closure of patent ductus arteriosus. To study the effect of INDO on cardiac output and mesenteric circulation, INDO was given by rectum (0.25 mg/kg, 0.5 mg/kg, 1.25 mg/kg--3 dogs in each group) and the control group received none. The cardiac output and organ blood flow were measured before and 1 hr after INDO with radioactive microspheres using 4 isotopes (Cr53, Ni95, Co57, Sn113). The blood flow to different parts of the GI tract was measured as percent of cardiac output using a gamma counter. Paired t test was used to calculate percent reduction in organ blood flow. During the experiment, there was no reduction in cardiac output in the entire group. Anesthesia had no effect on the control group. In the three INDO treated groups, percent reduction of mucosal blood flow of the stomach (63%, 32%, 68%, p less than 0.01), mid ileum (19%, 59%, 57%, p less than 0.05) and terminal ileum (57%, 35%, 54%, p less than 0.015) was significant. A strong trend in reduction of organ blood flow was noted in other regions. There was no significant change due to different dosages of INDO. The area of ischemia in this dog model corresponds to clinical pathology noted in necrotizing enterocolitis.