title: Dynamic changes of endothelin-1, nitric oxide, and cyclic GMP in patients with congenital heart disease.
abstract: BACKGROUND
  Pulmonary hypertension causes major morbidity and mortality after congenital heart surgery, but its mechanism remains unclear.
  
  
  RESULTS
  Plasma endothelin-1 (ET-1), nitric oxide (NO), and cyclic GMP (cGMP) were assayed at 6 intervals in 50 children undergoing cardiopulmonary bypass (CPB): before CPB, 10 minutes into CPB, and 0, 3, 6, and 12 hours after CPB. Three groups based on pulmonary flow and pressure were analyzed: low flow (LF, n=21), high flow/low pressure (systolic pulmonary pressure/systemic pressure ratio, Pp/Ps<50%, HF-LP, n=11), and high flow/high pressure (Pp/Ps> or =50%, HF-HP, n=19). HF-HP and HF-LP received alpha-blockers (chlorpromazine and/or prazosin). HF-HP patients received nitric oxide donors (nitroglycerin/sodium nitroprusside). ET-1 peaked at 6 hours, with its highest level in the HF-HP group (P<.01, by ANOVA). ET-1 correlated significantly with Pp/Ps at 6 hours (r2=.43, P<.005). In the HF-HP group, ET-1 remained above the other groups at 12 hours (12.7+/-2.5 pg/mL versus 6.4+/-1.1 pg/mL versus 6.5+/-3.8 pg/mL P<.05 by ANOVA). NO metabolites were elevated equivalently for the HF-HP and HF-LP groups (5.7+/-2.6 micromol/L versus 0.3.5+/-2.5 micromol/L at 12 hours, P=NS) despite nitric oxide donors and the excess ET-1 in HF-HP patients. Levels of cGMP were similarly elevated in HF-HP and HF-LP patients during this study.
  
  
  CONCLUSIONS
  Endogenous NO may decrease vascular tone and maintain low pulmonary pressure in HF-LP patients. High levels of ET-1, inadequate NO production, and/or impaired responses to NO may increase pulmonary pressure in HF-HP patients.
authors.affiliation: Section of Cardiothoracic Surgery, James W. Riley Hospital for Children and Indiana University Medical Center, Indianapolis 46202-5123, USA. kbando@wpo.iupui.edu
authors.forename: K
authors.initials: K
authors.lastname: Bando
authors.forename: P
authors.initials: P
authors.lastname: Vijayaraghavan
authors.forename: M W
authors.initials: MW
authors.lastname: Turrentine
authors.forename: T G
authors.initials: TG
authors.lastname: Sharp
authors.forename: G J
authors.initials: GJ
authors.lastname: Ensing
authors.forename: Y
authors.initials: Y
authors.lastname: Sekine
authors.forename: L
authors.initials: L
authors.lastname: Szekely
authors.forename: R J
authors.initials: RJ
authors.lastname: Morelock
authors.forename: J W
authors.initials: JW
authors.lastname: Brown
mesh_terms: D001794:Blood Pressure; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D006152:Cyclic GMP / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000601:surgery*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D007223:Infant; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D011183:Postoperative Complications / Q000209:etiology*
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; D006152:Cyclic GMP