title: Fetal-maternal nitrite exchange in sheep: Experimental data, a computational model and an estimate of placental nitrite permeability.
abstract: BACKGROUND
  Nitrite conveys NO-bioactivity that may contribute to the high-flow, low-resistance character of the fetal circulation. Fetal blood nitrite concentrations depend partly on placental permeability which has not been determined experimentally. We aimed to extract the placental permeability-surface (PS) product for nitrite in sheep from a computational model.
  
  
  METHODS
  An eight-compartment computational model of the fetal-maternal unit was constructed (Matlab(®) (R2013b (8.2.0.701), MathWorks Inc., Natick, MA). Taking into account fetal and maternal body weights, four variables (PS, the rate of nitrite metabolism within red cells, and two nitrite distribution volumes, one with and one without nitrite metabolism), were varied to obtain optimal fits to the experimental plasma nitrite profiles observed following the infusion of nitrite into either the fetus (n = 7) or the ewe (n = 8).
  
  
  RESULTS
  The model was able to replicate the average and individual nitrite-time profiles (r(2) > 0.93) following both fetal and maternal nitrite infusions with reasonable variation of the four fitting parameters. Simulated transplacental nitrite fluxes were able to predict umbilical arterial-venous nitrite concentration differences that agreed with experimental values. The predicted PS values for a 3 kg sheep fetus were 0.024 ± 0.005 l∙min(-1) in the fetal-maternal direction and 0.025 ± 0.003 l∙min(-1) in the maternal-fetal direction (mean ± SEM). These values are many-fold higher than the reported PS product for chloride anions across the sheep placenta.
  
  
  CONCLUSIONS
  The result suggests a transfer of nitrite across the sheep placenta that is not exclusively by simple diffusion through water-filled channels.
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Hobe J
authors.initials: HJ
authors.lastname: Schroeder
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kanda
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA; Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address: ablood@llu.edu.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
mesh_terms: D000818:Animals; D003198:Computer Simulation; D005260:Female; D007700:Kinetics; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008954:Models, Biological; D009573:Nitrites / Q000378:metabolism* / Q000493:pharmacokinetics; D010539:Permeability; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012756:Sheep
chemical_list: D009573:Nitrites
keywords: Nitrite; Placental transfer; Sheep; Simulation