title: Flow-induced release of endothelium-derived relaxing factor during pulsatile bypass: experimental study in the fetal lamb.
abstract: OBJECTIVE
  This study was initiated to test the hypothesis that fetal hemodynamic changes observed under pulsatile flow bypass might be related to the release of endothelium-derived relaxing factor through oscillating shear stress.
  
  
  METHODS
  Normothermic bypass was instituted in utero in 21 preterm fetal lambs for a 1-hour period through the right atrium and main pulmonary artery. Ultrasonic flowmeters were positioned around the descending aorta and the umbilical artery. The circuit consisted of an oxygenator and a pump set to either continuous flow (n = 7) or pulsatile flow (n = 7) and adjusted to maintain a fetal main arterial pressure of 50 mm Hg. In seven other animals, endothelium-derived relaxing factor was blocked by a continuous infusion of N omega-nitro-L-arginine after 30 minutes of pulsatile flow.
  
  
  RESULTS
  During the first 30 minutes of bypass, pump flows were significantly lower in the continuous-flow group than in the pulsatile-flow or blocked-flow groups (respectively, 612 +/- 144, 907 +/- 153 and 987 +/- 228 ml/min), with similar changes in aortic and umbilical flows. Systemic vascular resistances were significantly lower in the pulsatile-flow and blocked-flow groups than in the continuous-flow group (550 +/- 106 vs 821 +/- 212 dynes/sec/cm-5). However, after blockade of endothelium-derived relaxing factor, resistances increased gradually in the blocked-flow group to reach the level of that of the continuous-flow group at the end of bypass (943 +/- 77 vs 556 +/- 143 dynes/sec/cm-5 in the pulsatile-flow group).
  
  
  CONCLUSIONS
  Blockade of endothelium-derived relaxing factor after 30 minutes of pulsatile flow returns fetal hemodynamics to continuous flow conditions. The specific inhibitor of endothelium-derived relaxing factor used in this experiment suggests that nitric oxide may be released by fetal endothelium during pulsatile bypass.
authors.affiliation: Department of Cardiovascular Surgery, Hôpital Cardiologique, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Champsaur
authors.forename: C
authors.initials: C
authors.lastname: Vedrinne
authors.forename: S
authors.initials: S
authors.lastname: Martinot
authors.forename: F
authors.initials: F
authors.lastname: Tronc
authors.forename: J
authors.initials: J
authors.lastname: Robin
authors.forename: J
authors.initials: J
authors.lastname: Ninet
authors.forename: M
authors.initials: M
authors.lastname: Franck
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005318:Fetal Heart / Q000502:physiology; D005333:Fetus / Q000601:surgery*; D006439:Hemodynamics / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011673:Pulsatile Flow; D012756:Sheep; D013997:Time Factors; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D010100:Oxygen