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Dynamic changes of endothelin-1, nitric oxide, and cyclic GMP in patients with congenital heart disease
K Bando1, P Vijayaraghavan, M W Turrentine
1Section of Cardiothoracic Surgery, James W. Riley Hospital for Children and Indiana University Medical Center, Indianapolis 46202-5123, USA. kbando@wpo.iupui.edu
Insights
High endothelin-1 (ET-1) levels and inadequate nitric oxide (NO) may cause pulmonary hypertension after heart surgery. This study in children shows ET-1 increases with pulmonary pressure, while NO response is impaired in high-pressure cases.
Area of Science:
- Cardiovascular Physiology
- Pediatric Cardiology
- Surgical Outcomes Research
Background:
- Pulmonary hypertension is a significant complication following congenital heart surgery.
- The precise mechanisms driving post-cardiac surgery pulmonary hypertension remain incompletely understood.
Purpose of the Study:
- To investigate the roles of endothelin-1 (ET-1) and nitric oxide (NO) in the development of pulmonary hypertension after cardiopulmonary bypass (CPB).
- To analyze the relationship between ET-1, NO, and pulmonary pressure in pediatric patients undergoing CPB.
Main Methods:
- Assayed plasma ET-1, NO metabolites, and cyclic GMP (cGMP) in 50 children at multiple time points around CPB.
- Categorized patients into low flow (LF), high flow/low pressure (HF-LP), and high flow/high pressure (HF-HP) groups based on pulmonary hemodynamics.
- Administered alpha-blockers and NO donors to specific patient groups as clinically indicated.
Main Results:
- Endothelin-1 (ET-1) levels peaked 6 hours post-CPB, with significantly higher concentrations observed in the high flow/high pressure (HF-HP) group.
- ET-1 levels at 6 hours strongly correlated with the systolic pulmonary pressure/systemic pressure ratio (Pp/Ps).
- Despite NO donor administration, nitric oxide (NO) metabolites and cyclic GMP (cGMP) levels were similarly elevated in both HF-HP and high flow/low pressure (HF-LP) groups, suggesting potential impaired NO response in HF-HP.
Conclusions:
- Elevated ET-1, coupled with potentially inadequate NO production or response, likely contributes to increased pulmonary pressure in HF-HP patients.
- Endogenous NO may play a role in maintaining lower pulmonary pressure in HF-LP patients.
- Understanding these vasoactive pathways is crucial for managing post-operative pulmonary hypertension in pediatric cardiac surgery.
Background:
Pulmonary hypertension causes major morbidity and mortality after congenital heart surgery, but its mechanism remains unclear.
Methods And 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.