Coronary vasoconstriction mediated by endothelin-1 in neonates. Reversal by nitroglycerin

To determine the role of the vasoconstrictor peptide endothelin-1 in cardiopulmonary bypass in neonates, we measured plasma endothelin-1 concentrations in infants before and after cardiopulmonary bypass for arterial switch procedures and studied the effects of endothelin-1 on coronary tone and contractility in normal and reperfused neonatal pig hearts. Endothelin-1 blood concentrations (picograms per milliliter, mean +/- standard error) were significantly higher in neonates with arterial transposition and in umbilical venous blood (22.9 +/- 2.3 and 19.2 +/- 2.9, respectively) than in older children with atrial septal defects (13.2 +/- 1.6) or in healthy adults (10.7 +/- 2.5). After cardiopulmonary bypass, endothelin-1 concentrations increased 29% in neonates undergoing arterial switch procedure and 28% in children undergoing atrial septal defect repair (p < 0.05 versus before bypass). In isolated, blood-perfused neonatal pig hearts, endothelin-1 had dose-related coronary constrictor and inotropic effects between 25 and 100 pmol. Endothelin-1 concentrations that did not increase coronary perfusion pressure (5 to 10 pmol) caused significant coronary constriction in the presence of norepinephrine (10 nmol/L). During reperfusion after 30 minutes of global normothermic ischemia, the coronary vasoconstrictor effects of both endothelin-1 alone and endothelin-1 plus norepinephrine were significantly enhanced. Nitroglycerin reversed vasoconstriction produced by endothelin-1 and endothelin-1 plus norepinephrine both before and after ischemia-reperfusion. We conclude that endothelin-1 concentrations are significantly elevated in neonates and are further increased after cardiopulmonary bypass. Coronary vasoconstriction caused by endothelin-1 is enhanced by ischemia-reperfusion and by norepinephrine present in concentrations typically observed after neonatal cardiopulmonary bypass. Nitroglycerin reverses coronary vasoconstriction induced by endothelin-1 and may therefore be beneficial in the postoperative management of neonates after cardiac operations.