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.
McGowan
F X
FX
Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, Pa.
Davis
P J
PJ
Siewers
R D
RD
del Nido
P J
PJ
D000328:Adult; D000818:Animals; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D003331:Coronary Vessels / Q000502:physiology*; D016232:Endothelins / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D005996:Nitroglycerin; D009638:Norepinephrine