title: Role of nitric oxide pathway in placental dysfunction following fetal bypass.
abstract: BACKGROUND
  The etiology of placental dysfunction after fetal cardiopulmonary bypass remains unknown. The placental nitric oxide (NO) pathway has been implicated in this pathophysiology. We set out to examine possible perturbations in this pathway in an ovine model of fetal bypass.
  
  
  METHODS
  Ovine fetuses (n = 14) between 100 and 114 days of gestation, instrumented to measure hemodynamics and umbilical blood flow, were placed on bypass for 30 minutes and followed after bypass for 2 hours. Sham controls (n = 6) were instrumented but did not undergo bypass. Real-time, in-vivo NO concentrations were measured in the placental circulation. To examine other components of the NO pathway, fetal plasma samples were analyzed by immunoassays for total NO metabolite and cyclic guanosine 3',5'-cyclic monophosphate (cGMP) levels. In addition, the expression of phosphodiesterase-5 was examined in placenta by immunohistochemistry. Statistical analysis was performed using analysis of variance with least significant difference post hoc tests (p < or = 0.05).
  
  
  RESULTS
  With the onset of bypass, an immediate increase occurs in umbilical NO concentrations. These return to baseline with cessation of bypass, and decline thereafter. In contrast, there was a linear increase in fetal plasma cGMP levels and a decline in NO metabolite concentrations through the post-bypass period. There was a dramatic increase in placental phosphodiesterase-5 expression with 30 minutes of bypass. The changes occur simultaneously with decreasing umbilical flows, increased placental vascular resistance, and worsening placental gas exchange.
  
  
  CONCLUSIONS
  Fetal bypass leads to significant reductions in placental NO concentrations despite increases in fetal plasma cGMP and placental phosphodiesterase-5 levels, indicative of perturbations in the fetal-placental NO pathway.
authors.affiliation: Division of Cardiothoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lam
authors.forename: R Scott
authors.initials: RS
authors.lastname: Baker
authors.forename: Jerri
authors.initials: J
authors.lastname: McNamara
authors.forename: Robert
authors.initials: R
authors.lastname: Ferguson
authors.forename: John
authors.initials: J
authors.lastname: Lombardi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Clark
authors.forename: Pirooz
authors.initials: P
authors.lastname: Eghtesady
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000032:analysis; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D006152:Cyclic GMP / Q000097:blood; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005260:Female; D005333:Fetus / Q000601:surgery*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D010920:Placenta / Q000503:physiopathology*; D010922:Placenta Diseases / Q000209:etiology* / Q000503:physiopathology; D011183:Postoperative Complications / Q000209:etiology*; D011247:Pregnancy; D012756:Sheep; D015398:Signal Transduction
chemical_list: D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D009569:Nitric Oxide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP; D010100:Oxygen