title: Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow.
abstract: BACKGROUND
  After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow.
  
  
  RESULTS
  Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25 degrees C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P:<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P:<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to approximately 70% of pre-CPB levels in both control and shunt lambs (P:<0.05). Total NOS activity and endothelial NOS protein levels were unchanged.
  
  
  CONCLUSIONS
  Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.
authors.affiliation: Department of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA 94143-0106, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: McMullan
authors.forename: J M
authors.initials: JM
authors.lastname: Bekker
authors.forename: A J
authors.initials: AJ
authors.lastname: Parry
authors.forename: M J
authors.initials: MJ
authors.lastname: Johengen
authors.forename: A
authors.initials: A
authors.lastname: Kon
authors.forename: R S
authors.initials: RS
authors.lastname: Heidersbach
authors.forename: S M
authors.initials: SM
authors.lastname: Black
authors.forename: J R
authors.initials: JR
authors.lastname: Fineman
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000209:etiology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000000981:diagnostic imaging; D011652:Pulmonary Circulation; D012756:Sheep; D014463:Ultrasonography
chemical_list: D009566:Nitrates; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP