Selective Elevation of Systemic Blood Pressure by Epinephrine during Sepsis-Induced Pulmonary Hypertension in Piglets

Meadow, William; Rudinsky, Brian; Strates, Elene

doi:10.1203/00006450-198609000-00013

Cited by 20 publications

(11 citation statements)

References 22 publications

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“…Previously, EP has been shown to have variable effects on the pulmonary vasculature. Consistent with our findings, other investigators have reported a significant decrease in PVR during EP infusion in piglets (29,30). Doses in these studies ranged from 0.2 to 15 g/kg/min.…”

Section: Catecholamine Administrationsupporting

confidence: 81%

Right Ventricular Injury in Young Swine: Effects of Catecholamines on Right Ventricular Function and Pulmonary Vascular Mechanics

et al. 2000

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Acute right ventricular (RV) injury is commonly encountered in infants and children after cardiac surgery. Empiric medical therapy for these patients results from a paucity of data on which to base medical management and the absence of animal models that allow rigorous laboratory testing. Specifically, exogenous catecholamines have unclear effects on the injured right ventricle and pulmonary vasculature in the young. Ten anesthetized piglets (9 -12 kg) were instrumented with epicardial transducers, micromanometers, and a pulmonary artery flow probe. RV injury was induced with a cryoablation probe. Dopamine at 10 g/kg/min, dobutamine at 10 g/kg/min, and epinephrine (EP) at 0.1 g/ kg/min were infused in a random order. RV contractility was evaluated using preload recruitable stroke work. Diastolic function was described by the end-diastolic pressure-volume relation, peak negative derivative of the pressure waveform, and peak filling rate. In addition to routine hemodynamic measurements, Fourier transformation of the pressure and flow waveforms allowed calculation of input resistance, characteristic impedance, RV total hydraulic power, and transpulmonary vascular efficiency. Cryoablation led to a stable reproducible injury, decreased preload recruitable stroke work, and impaired diastolic function as measured by all three indices. Infusion of each catecholamine improved preload recruitable stroke work and peak negative derivative of the pressure waveform. Dobutamine and EP both decreased indices of pulmonary vascular impedance, whereas EP was the only inotrope that significantly improved transpulmonary vascular efficiency. Although all three inotropes improved systolic and diastolic RV function, only EP decreased input resistance, decreased pulmonary vascular resistance, and increased transpulmonary vascular efficiency. Abbreviations RV, right ventricle DA, dopamine DB, dobutamine EP, epinephrine PRSW, preload recruitable stroke work EDPVR, end-diastolic pressure-volume relationship Kc, right ventricular chamber stiffness dP/dt min , peak negative value of the RV pressure waveform derivative Qpk, peak filling rate TVE, transpulmonary vascular efficiency PA, pulmonary artery PVR, pulmonary vascular resistance Acute RV injury is encountered in infants and children with congenital heart disease after cardiac surgery (1). Despite its frequent occurrence, the ideal therapeutic strategy to manage the young patient with acute RV systolic and/or diastolic dysfunction remains unknown. The management of infants and children with RV dysfunction in the intensive care unit is centered on providing adequate oxygen delivery through manipulations of the cardiac and respiratory systems. Techniques used to augment cardiac output after RV injury include inotropic support and manipulation of loading conditions (2, 3). Despite widespread use of inotropes, little is known about their detailed interactions on RV systolic function (2), RV diastolic function, and the pulmonary vasculature (4). Although these drugs may enhance intrinsic RV ...

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Section: Catecholamine Administrationsupporting

confidence: 81%

Right Ventricular Injury in Young Swine: Effects of Catecholamines on Right Ventricular Function and Pulmonary Vascular Mechanics

et al. 2000

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“…However this approach has not yet been systematically investigated. The data of Meadow et al (3) for the newborn pig suggest that large doses are necessary to accomplish a significant increase in systemic vascular resistance. In their study, a significant increase in Qp was observed during administration of as much as 15 pg/kg/min of epinephrine, a dose much greater than presently recommended for use in newborn infants (8).…”

Section: Discussionmentioning

confidence: 98%

“…Meadow et al (3) reported that after group B streptococcusinduced pulmonary hypertension in the piglet, a significant increase in Qp can be achieved by elevating the PSA Although not evaluated in their experimental animals, Meadow et al also suggested that a selective elevation of the PsA during pulmonary hypertension could also impede right to left shunt at the foramen ovale and thus improve oxygenation (3). Furthermore, in adult animals with RVH and decreased Qp, an elevation in PSA increases cardiac output (4)(5)(6).…”

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confidence: 99%

The Effect of an Increase in Systemic Arterial Pressure in the Newborn with Right Ventricular Hypertension

Belik

Baron

1990

Pediatr Res

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ABSTRACT. To evaluate the effect of an elevation in systemic arterial pressure upon pulmonary blood flow and arterial oxygenation during right ventricular hypertension (RVH), we acutely studied 13 1-d-old piglets. Catheters were positioned in the pulmonary artery, both atria, and the aorta for hemodynamic measurements. An electromagnetic probe was positioned in the main pulmonary artery for pulmonary blood flow measurement. Systemic and regional blood flow were measured with the radiolabeled microsphere technique. A balloon-mounted catheter was advanced in the aorta and maintained at the lower thoracic level. After induction of RVH (pulmonary artery banding), a significant decrease in arterial 0 2 pressure from 54.4 f 1.6 to 10.6 2 0.4 kPa (p < 0.01), a 30% reduction in systemic arterial pressure, and a 44% decrease in pulmonary blood flow were observed. During RVH, partial inflation of the aortic balloon to restore the systemic arterial pressure to its initial value led to an increase in arterial O2 pressure to 23.5 2 3.1 kPa ( p < 0.01). Full inflation of the balloon further increased the arterial O2 pressure to 32.6 f 2.9 kPa ( p < 0.01). Aortic balloon inflation increased pulmonary blood flow in 11 and systemic O2 delivery in nine of the 13 animals. RVH was associated with a significant increase in cerebral and right ventricular myocardial free-wall blood flow and a decrease in renal and bowel blood flow and O2 delivery (p < 0.01). Aortic balloon inflation during RVH did not change either the cerebral or myocardial free-wall blood flow, but further significantly decreased renal and bowel blood flow and O2 delivery. In conclusion, an elevation in systemic arterial pressure significantly reduces foramen ovale shunt and increases pulmonary blood flow and systemic O2 delivery in the newborn pig with RVH. This finding may prove useful in the clinical management of hypoxemic infants with persistent pulmonary hypertension syndrome. (Pediatr Res 28: 603-608, 1990 PPHN, persistent pulmonary hypertension syndrome Pao2, arterial O2 pressureIn the newborn pig, we have previously shown that RVH is associated with a significant decrease in PSA and cardiac output (1,2). The factors responsible for the reduction in cardiac output during RVH are presently unclear, but previously reported data suggest that the reduction is related to the changes in PSA (3-6). Meadow et al. (3)reported that after group B streptococcusinduced pulmonary hypertension in the piglet, a significant increase in Qp can be achieved by elevating the PSA Although not evaluated in their experimental animals, Meadow et al. also suggested that a selective elevation of the PsA during pulmonary hypertension could also impede right to left shunt at the foramen ovale and thus improve oxygenation (3). Furthermore, in adult animals with RVH and decreased Qp, an elevation in PSA increases cardiac output (4-6).In infants, the PPHN syndromeis associated with hypoxemia related not only to the decreased Qp, but also to the magnitude of the right to left shunt across ...

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“…(3). We can thus compare the results of our high-dose infusions with the lowest dose used in their study.…”

Section: Discussionmentioning

confidence: 99%

The Circulatory Effects of Epinephrine Infusion in the Anesthetized Piglet

Barrington

Chan

1993

Pediatr Res

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ABSTRAn. There are few published data regarding the circulatory effects of systemic epinephrine infusions in newborn subjects. We therefore instrumented six piglets aged 5 to 10 d while they were under pentobarbitone anesthesia for determination of cardiac output, left anterior descending coronary artery flow, systemic and pulmonary pressures, and mixed venous, arterial and coronary sinus gases. Systemic, coronary, and pulmonary vascular resistances, coronary oxygen consumption, and myocardial oxygen extraction ratio were calculated. Epinephrine was infused at doses from 0.2 to 3.2 pg/kg/min doubling at 15-min intervals, and measurements were taken after stability had been obtained. Cardiac o u t~u t increased at the lowest dose investigated, i.e. 0.2 pg/kg/min, and progressively increased as the dose was advanced up to 1.6 pglkglrnin, decreasing significantly at 3.2 pg/kg/min. Blood increased progressively, being significantly above baseline at 0.8, 1.6, and 3.2 pg/kg/min and having increased by approximately 81% at the highest dose investigated. Pulmonary arterial pressures were also increased at 1.6 and 3.2 pg/kg/min, but only by 35% at the highest dose of 3.2 pg/kg/min. Systemic and pulmonary vascular resistances both decreased at the three lower doses investigated and then began to increase progressively; however, the systemic vascular resistance increased to a significantly greater degree than pulmonary vascular resistance. Coronary oxygen consumption increased progressively as the epinephrine dose was increased; however, coronary blood flow and coronary oxygen delivery increased more than oxygen consumption, leading to a progressive reduction in myocardial oxygen extraction ratio and a progressive increase in coronary sinus oxygen content. Whole-body oxygen consumption was increased, but to a lesser extent than systemic oxygen transport. We conclude that, at low doses, epinephrine is a potent inotrope and a systemic and pulmonary vasodilator in the newborn piglet. With progressive increases in the dose, systemic vasoconstriction is significantly greater than pulmonary. Increasing cardiac oxygen demands are oversupplied by increases in coronary blood flow. fusions are occasionally used as a back-up inotropic therapy for sick newborn infants (l), particularly those with persistent pulmonary hypertension of the newborn. In such infants, pulmonary vascular resistance is elevated and cardiac output is low (2). A drug that has selective pulmonary vasodilating or selective systemic pressor and positive inotropic properties would therefore be of great value. One previous study of the effects of highdose epinephrine infusions (3.5, 7, and 15 pg/kg/min) (3) in newborn piglets with group B streptococcus-induced pulmonary hypertension suggested a selective systemic pressor effect. To obtain additional information regarding the effects of this mode of therapy, the following study was performed to determine the effects of epinephrine infusions at lower, clinically applicable doses in healthy, acutely instrumented pigle...

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Selective Elevation of Systemic Blood Pressure by Epinephrine during Sepsis-Induced Pulmonary Hypertension in Piglets

Cited by 20 publications

References 22 publications

Right Ventricular Injury in Young Swine: Effects of Catecholamines on Right Ventricular Function and Pulmonary Vascular Mechanics

Right Ventricular Injury in Young Swine: Effects of Catecholamines on Right Ventricular Function and Pulmonary Vascular Mechanics

The Effect of an Increase in Systemic Arterial Pressure in the Newborn with Right Ventricular Hypertension

The Circulatory Effects of Epinephrine Infusion in the Anesthetized Piglet

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