RESUMO
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.
Assuntos
Vasos Coronários/fisiologia , Endotelinas/fisiologia , Coração/fisiopatologia , Nitroglicerina/farmacologia , Vasoconstrição/efeitos dos fármacos , Adulto , Animais , Ponte Cardiopulmonar , Pré-Escolar , Endotelinas/sangue , Endotelinas/farmacologia , Feminino , Hemodinâmica , Humanos , Recém-Nascido , Masculino , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica , Norepinefrina/farmacologia , SuínosRESUMO
Optimal methods of myocardial preservation remain controversial in the neonate. This study compared prolonged hypothermic storage of neonatal hearts with modified University of Wisconsin solution (group I) with a solution formulated to promote anaerobic glycolysis by providing proton buffering with histidine (100 mmol/L) and exogenous glucose and insulin (group II). Hearts from piglets aged 3 to 5 days were given a single dose of either solution (n = 6 each), subjected to 20 hours of global ischemia at 4 degrees C, and reperfused with an erythrocyte-enhanced perfusate in an isovolumic Langendorff preparation. After 1 hour of reperfusion, in comparison with hearts preserved with University of Wisconsin solution, those in group II demonstrated (mean +/- standard error of the mean) greater left ventricular developed pressure (101 +/- 7 versus 62 +/- 9 mm Hg, p < 0.01) and the first derivative of left ventricular pressure (816 +/- 23 versus 614 +/- 69 mm Hg.sec-1, p < 0.05). Diastolic indices were reduced to a similar degree in the two groups. Myocardial oxygen consumption was significantly greater (38.8 +/- 2.4 versus 11.8 +/- 2.4 microliters oxygen.min.g-1, p < 0.01) in group II hearts. Group I hearts vasoconstricted (6% increase in coronary vascular resistance) in response to an intracoronary infusion of acetylcholine (20 nmol.min-1); in contrast, acetylcholine produced coronary dilation in group II hearts (5% decrease in coronary resistance, p < 0.02) that was similar to that observed in nonischemic control hearts. These results demonstrate enhanced preservation of myocardial contractility, oxidative metabolism, and vascular function in neonatal hearts provided by a solution designed to buffer protons and promote anaerobic glycolysis during ischemia.
Assuntos
Soluções Cardioplégicas , Coração , Preservação de Órgãos/métodos , Animais , Animais Recém-Nascidos , Vasos Coronários/fisiologia , Glicólise , Técnicas de Cultura de Órgãos , Suínos , Resistência VascularRESUMO
Lung injury remains an important problem after cardiopulmonary bypass. The contribution of altered surfactant concentration or activity to pulmonary dysfunction after cardiopulmonary bypass is unclear. Recent evidence indicates that alveolar surfactant exists in specific aggregate forms that differ with respect to density, phospholipid composition, and function. A transition from surface active, higher density, large aggregates of surfactant to lower density, small aggregates that possess reduced surface activity has been demonstrated after experimental lung injury. The purpose of the present study was to examine surfactant aggregate fractions before and after bypass in children. Twelve acyanotic patients, aged 2 to 12 years, underwent intraoperative pulmonary function testing followed by bronchoalveolar lavage before incision and approximately 1 hour after termination of cardiopulmonary bypass. Saturated phosphatidylcholine pool sizes and total protein content of the small- and large-aggregate fractions of bronchoalveolar lavage fluid were determined. One hour after termination of cardiopulmonary bypass, the ratio of saturated phosphatidylcholine in small-aggregate as compared with that in large-aggregate fractions increased (mean +/- standard error) from 0.19 +/- 0.03 to 0.37 +/- 0.07 (p < 0.02), as did the ratio of saturated phosphatidylcholine to protein in the small-aggregate fraction (from 0.04 +/- 0.01 to 0.08 +/- 0.02, p < 0.05). Reductions in forced vital capacity (-19% +/- 5%), inspiratory capacity (-15% +/- 3%), and small airway flow rates (-32% +/- 6%) were also observed after bypass. These changes were accompanied by a fivefold increase in alveolar polymorphonuclear leukocyte content. The present study suggests that cardiopulmonary bypass of moderate duration in relatively healthy children is associated with surfactant changes that are similar in type and magnitude to those observed in experimental lung injury.