Effects of Ibuprofen and Indomethacin on the Regional Circulation in Newborn Piglets

Abstract

We investigated the effects of clinically comparable doses of ibuprofen and indomethacin on renal, gastrointestinal and cerebral perfusion in newborn piglets, and hypothesized that ibuprofen would have less effect on regional circulation. Animals were randomly assigned to receive ibuprofen (20 mg/kg, n = 8), indomethacin (0.3 mg/kg, n = 7) or vehicle (n = 6). Fluorescent microspheres were injected prior to and at 20, 40, 60, 90 and 120 min after drug administration. Regional blood flow was measured and vascular resistances were calculated. Cardiovascular and respiratory variables were not significantly affected by either study drug or vehicle. Ibuprofen increased renal cortical and medullary resistance by 44 and 52% (p < 0.05). However, ibuprofen had no significant effects on gastrointestinal or cerebral resistance. Indomethacin raised renal cortical and medullary resistance by 66 and 71% at 60 min postinjection, respectively (p < 0.05). Indomethacin increased duodenojejunal, ileal and colon resistance by 97, 102 and 75% at 60 min, respectively (p < 0.05). Indomethacin increased cerebral cortical and cerebellar resistance by 92 and 86% at 90 min (p < 0.05). While indomethacin and, to a lesser extent, ibuprofen both increase renal vascular resistance, indomethacin vasoconstricts the gastrointestinal and cerebral circulations which are unaffected by ibuprofen.

Effects of ibuprofen treatment on the developing preterm baboon kidney

“…NSAID treatment increases renal vascular resistance, reduces renal blood flow (14,30), decreases glomerular filtration rate (1,22), and is an independent risk factor for the development of acute renal failure (4). Similarly, NOS inhibition has been shown to significantly reduce renal blood flow, glomerular filtration rate, and alter tubular function in neonatal animals (27).…”

Glucagon-like peptide-2 acutely increases proximal small intestinal blood flow in TPN-fed neonatal piglets

“…The use and technical aspects of the FMS [FluoSpheres Blood Flow Determination Kits #2 (F-8891), Molecular Probes, Eugene, OR] have been previously described (25,27,30). In short, FMS were injected directly into the heart via the carotid catheter to ensure adequate mixing.…”

“…Using these values, we estimated the superior mesenteric artery (SMA) blood flow as the sum of blood flows to the PJ, DJ, PI, DI, and PC, whereas the celiac blood flow was calculated by summing the flows to the stomach, duodenum, pancreas, spleen, and liver. For each piglet, we also calculated the mean organ blood flow rates across the four time points (15,30,45, and 120 min); this value was expressed as an absolute rate (ml/min) and relative to the time 0 baseline flow (%baseline).…”

“…Differences among segments were tested using a post hoc Tukey's test. We then tested for differences in the absolute and relative blood flow rates between the baseline and the mean GLP-2-treated value estimated from all four time-points (15,30,45, and 120 min) ( Table 1, Fig. 2).…”

“…In previous studies, radioactive and fluorescent microsphere deposition has been used to quantitate the effects of hormones and other agents on blood flow to GI tissues or organs (8,9,11,26,30). Therefore, the aim of the current study was to determine the effect of acute GLP-2 infusion on the distribution of blood flow in GI and other visceral organs in TPN-fed neonatal piglets using the fluorescent microsphere deposition method.…”