title: Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation.
abstract: Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n=9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P<0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E(2). SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.
authors.affiliation: Department of Physiology, Monash University, Clayton, Vic. 3168, Australia.
authors.forename: Micka C
authors.initials: MC
authors.lastname: Bertucci
authors.forename: Jan M
authors.initials: JM
authors.lastname: Loose
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Miller
mesh_terms: D028341:Activins / Q000032:analysis / Q000097:blood; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015232:Dinoprostone / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005311:Fetal Hypoxia / Q000188:drug therapy* / Q000209:etiology*; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000032:analysis; D008026:Ligation; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D012756:Sheep; D012460:Sulfasalazine / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014469:Umbilical Arteries / Q000601:surgery*
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins; D012460:Sulfasalazine; D015232:Dinoprostone; D010100:Oxygen