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J Thorac Cardiovasc Surg 1995;109:88-98
© 1995 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

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

Pittsburgh, Pa.

Supported in part by the B. B. Sankey Anesthesia Advancement Award from the International Anesthesia Research Society (F.X.M.), National Institutes of Health grant HL 46207 (P.J.d.N.) and the Children's Hospital of Pittsburgh.

Address for reprints: Francis X. McGowan, Jr., MD, Children's Hospital of Pittsburgh, Department of Anesthesiology, 3705 Fifth Ave. at DeSoto St., Pittsburgh, PA 15213-2583.

Abstract

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. (J THORAC CARDIOVASC SURG 1995; 109:88-98)

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