Inotropic Response of the Neonatal Canine Myocardium to Dopamine

Driscoll, David J.; Gillette, Paul C.; Ezrailson, Edward G.; Schwartz, Arnold

doi:10.1203/00006450-197801000-00011

Cited by 63 publications

(13 citation statements)

References 7 publications

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“…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.…”

Section: Discussionsupporting

confidence: 67%

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

Gleason

Robinson

Harris

et al. 2002

Journal of Applied Physiology

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man. Cerebrovascular effects of intravenous dopamine infusions in fetal sheep. J Appl Physiol 92: 717-724, 2002; 10.1152/japplphysiol.00600.2001.-Preterm infants are often treated with intravenous dopamine to increase mean arterial blood pressure (MAP). However, there are few data regarding cerebrovascular responses of developing animals to dopamine infusions. We studied eight near-term and eight preterm chronically catheterized unanesthetized fetal sheep. We measured cerebral blood flow and calculated cerebral vascular resistance (CVR) at baseline and during dopamine infusion at 2.5, 7.5, 25, and 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 . In preterm fetuses, MAP increased only at 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 (25 Ϯ 5%), whereas in near-term fetuses MAP increased at 25 g ⅐ kg Ϫ1 ⅐ min Ϫ1 (28 Ϯ 4%) and further at 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 (51 Ϯ 3%). Dopamine infusion was associated with cerebral vasoconstriction in both groups. At 25 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , CVR increased 77 Ϯ 51% in preterm fetuses and 41 Ϯ 11% in near-term fetuses, and at 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , CVR increased 80 Ϯ 33% in preterm fetuses and 83 Ϯ 21% in near-term fetuses. We tested these responses to dopamine in 11 additional near-term fetuses under ␣-adrenergic blockade (phenoxybenzamine, n ϭ 5) and under dopaminergic D1-receptor blockade (SCH-23390, n ϭ 6). Phenoxybenzamine completely blocked dopamine's pressor and cerebral vasoconstrictive effects, while D1-receptor blockade had no effect. Therefore, in unanesthetized developing fetuses, dopamine infusion is associated with cerebral vasoconstriction, which is likely an autoregulatory, ␣-adrenergic response to an increase in blood pressure.brain; fetus; vasoconstriction BLOOD PRESSURE IS AN IMPORTANT "vital sign" that is carefully monitored in preterm infants. Hypotension is believed to be an important risk factor for cerebral ischemic injury and intracranial hemorrhage, and so preterm infants often receive volume expanders (even in the absence of hypovolemia) and/or inotropic drugs (most commonly, dopamine) to increase blood pressure (1, 18). However, concern has been raised about whether these management practices could be detrimental (29). Seri et al. (25) recently reported that low-dose dopamine infusion does not affect cerebral blood flow (CBF) velocity in sick, normotensive preterm infants. However, little else is known about the cerebrovascular responses of the developing brain to intravenous dopamine and/or acute increases in blood pressure. In adult animals, intravenous dopamine at moderate doses causes cerebral vasodilation, presumably by stimulation of specific vasodilatory dopaminergic receptors (32). 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)....

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Section: Discussionsupporting

confidence: 67%

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

Gleason

Robinson

Harris

et al. 2002

Journal of Applied Physiology

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“…The inotropic effect of dopamine, therefore, is dependent on 1) the integrity of the adrenergic receptor, 2) the extent of sympathetic innervation of the myocardium, 3) availability of norepinephrine stores in the presynaptic terminal, and 4) the number of contractile elements of the myocyte. We found, as have others (2,15), that the inotropic response to dopamine infusion was blunted in the very young animal suggesting that one or more of these factors may be deficient.…”

Section: Effects Of Dopumine Infusionsupporting

confidence: 66%

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

et al. 1987

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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...

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“…21], Vagotomized 6-to 12-day-old dogs given 1, 10 or 100pg/kg dopamine i.v. did not respond to the smallest dose and required 10 pg/kg for a pressor ef fect and 100 pg/kg for tachycardia [21], The inotropic response of isolated ventricular myocardium to dopamine was found to in crease with increasing age in dogs from birth to adult levels of contractile force at 21-33 days after birth [12], Infusion of dopa mine (2-50 pg/kg/min) in a group of 3-to 65-day old dogs was accompanied by increased arterial pressure, heart rate and cardiac out- put [ 13]. As in our study, these investigations were carried out under anesthesia with pento barbital, but a dose of 30 mg/kg was used at all ages in contrast to smaller doses that we used in younger animals (table I).…”

Section: Discussionmentioning

confidence: 99%

“…The other cate cholamine of interest in the regulation of the peripheral circulation, dopamine, has been studied with respect to cardiac actions [12,13,21] and renal circulatory effects [13] in neonatal dogs anesthetized with pentobarbi tal. However, among the mammals, the dog is relatively immature at birth [16].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Effects of Dopamine in Developing Swine

Buckley¹,

Brazeau²,

Frasier³

1983

Neonatology

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Cardiac function and peripheral blood flows were measured before and during single intravenous injections of dopamine (2–25 μg/kg) in developing and mature swine anesthetized with pentobarbital. A positive inotropic effect was observed in even the youngest swine. Renal vasoconstriction was observed even after low doses of dopamine in animals younger than 1 month of age, and femoral vasoconstriction in animals younger than 2 weeks of age, unless α-adrenergic receptors were blocked by phentolamine. We concluded that the vasodilator responses to dopamine are slower to develop in the renal than in the femoral circulation.

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Inotropic Response of the Neonatal Canine Myocardium to Dopamine

Cited by 63 publications

References 7 publications

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

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

Cardiovascular Effects of Dopamine in Developing Swine

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