The Effects of Dopamine Infusion on Regional Blood Flow in Newborn Lambs

Abstract

ABSTRACT. The purpose of this project was to investigate the effects of high rates of dopamine infusion on cardiac output and regional blood flow in the lamb. We studied eight unanesthetized newborn lambs (mean age 7 + 2 days) during a 15-min baseline period and while infusing dopamine at 5-, 20-, 80-, and 160 pg/kg/min. We measured cardiac output and mean aortic, pulmonary arterial and left atrial pressures, and organ blood flow using radionuclidelabeled microspheres at each rate of dopamine infusion. Cardiac output increased significantly with increasing rates of infusion up to 80 pg/kg/min but decreased at 160 pg/kg/ min. Aortic, pulmonary arterial, and left atrial pressures increased at rates of infusion above 5 pg/kg/min. Blood flow to all organs was unchanged at the 5 pg/kg/min rate of infusion of dopamine while blood flow to the brain and heart increased at the 80 pg/kg/min rate of infusion and blood flow to the gut and kidney decreased. We conclude that dopamine is an effective inotropic agent in the newborn lamb but that an inotropic:afterload mismatch exists at high infusion rates. Despite an increase in cardiac output at low rates of infusion, dopamine did not selectively vasodilate the vascular bed of any organs tested. Furthermore, at high rates of infusion dopamine actually impaired blood flow to the gut and kidney. (Pediatr Res 21: 131-136, 1987) Dopamine remains an extensively used catecholamine in the management of shock in critically ill infants and children (1). We recently studied the effects of dopamine on hemodynamics in 2-to 3-wk-old lambs and found it to be an effective inotropic agent (2). However, inherent properties of neonatal myocardium may render it relatively unresponsive to the inotropic actions of dopamine and the same effects may not occur in the younger lamb. In the clinical setting, myocardial immaturity may prompt the use of rates of infusion of dopamine in excess of those currently recommended (1). The effects of high rates of infusion on regional blood flow in the newborn are unknown.The purpose of our study was to investigate the effects of dopamine on regional blood flow in newborn lambs over a wide range of infusion rates. We hypothesized that in the newborn lamb dopamine would not increase cardiac output at conventionally used rates of infusion but might at higher rates. At these higher rates, however, we anticipated that the a-adrenergic effect of dopamine would compromise blood flow to vital organs. MATERIALS AND METHODSSurgical preparations. We operated on eight lambs using halothane and nitrous oxide anesthesia delivered by a piston type ventilator. From a left hindlimb cutdown we inserted polyvinyl catheters into a peripheral artery and vein and advanced them into the descending aorta and inferior vena cava, respectively. We also inserted a 3.5 Fr thermistor wire (Edwards Laboratories, Inc., Irvine, CA) into a peripheral artery by separate hindlimb cutdown and advanced it into the descending aorta. Finally, we placed a polyvinyl catheter in a forelimb artery and ad...

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

“…The cardiovascular effects of dopamine that we observed are consistent, in part, with studies in developing animals suggesting that neonates exhibit relative insensitivity to inotropes, believed to be due to immaturity of cardiac ␤ 1 -adrenergic receptor activity (5,6,8,12,31). In human infants, the cardiovascular effects of dopamine are less consistent, presumably because of the variable physiology of critically ill neonates who require or receive pressors.…”

“…In immature animals, dopamine is a less effective inotropic agent, presumably because of immaturity of cardiac ␤ 1 -adrenergic receptors. Minimal cerebral vasodilatory, or possibly vasoconstrictive, effects might therefore be expected at low or moderate dopamine doses, because development of vascular dopaminergic receptors is also likely to be incomplete, particularly compared with ␣-adrenergic receptors (8,12,30,31).The objective of this study was to describe the cerebrovascular responses of developing fetuses at two gestational ages to increasing doses of intravenous dopamine with and without ␣-adrenergic or dopaminergic (D 1 ) receptor blockade. We tested the hypothesis that dopamine causes dose-dependent cerebral vasoconstriction and that this response may be enhanced because of immaturity of dopaminergic receptor development and increased sensitivity and activation of ␣-adrenergic receptors.…”

“…In immature animals, dopamine is a less effective inotropic agent, presumably because of immaturity of cardiac ␤ 1 -adrenergic receptors. Minimal cerebral vasodilatory, or possibly vasoconstrictive, effects might therefore be expected at low or moderate dopamine doses, because development of vascular dopaminergic receptors is also likely to be incomplete, particularly compared with ␣-adrenergic receptors (8,12,30,31).…”

Chloralose Alters Both Basal Hemodynamics and Cardiovascular Responses to Alveolar Hypoxia in Chronically Instrumented, Spontaneously Breathing Lambs'

“…Preload, represented by mean left atrial pressure, did not differ between treatment groups. However, the chloralose-treated group demonstrated increased afterload, indicated by increased systemic vascular resistance, to levels that impair cardiac output both in constantly perfused lamb hearts (16) and in conscious neonatal lambs (17). Therefore, the failure of cardiac output to rise in response to alveolar hypoxia in chloralose-treated lambs must be explained by relationships between hypoxia, increased afterload, and/or reduced contractility.…”

Indomethacin Does Not Alter the Circulating Catecholamine Response to Asphyxia in the Neonatal Piglet

“…D levels of 500-750 pg/ml, which are similar to those measured in the present study, have been reported in two recent studies of stressed human newborns (18,19). Results of exogenous D infusions in neonatal lambs suggest that these levels are probably not hemodynamically significant (20). The source of catecholamines in the neonatal circulation is uncertain.…”