Dynamic changes of endothelin-1, nitric oxide, and cyclic GMP in patients with congenital heart disease

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≥50%, HF-HP, n=19). HF-HP and HF-LP received α-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-I correlated significantly with Pp/Ps at 6 hours (P=.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 μmol/L versus 0.3.5±2.5 μmol/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.