Effects of high plasma epinephrine and Ca2+ concentration on newborn myocardial function following ischemia

Caspi, Joseph; Coles, John G.; Benson, Lee; Herman, S L; Augistine, Janet; Tsao, Peter W.; Brezina, A.; Kolín, A; Wilson, Gregory J.

doi:10.1016/0022-2828(90)91658-t

Cited by 6 publications

(7 citation statements)

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“…In this model, the measured plasma levels of E and NOR were comparable with those obtained from newborns with congenital heart defects before surgery (30). Catecholamine injury has recently been delineated in cultures of adult cardiac muscle (31).…”

Section: Discussionsupporting

confidence: 61%

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Heart Rate Independence of Catecholamine-Induced Myocardial Damage in the Newborn Pig

et al. 1994

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Neonates undergoing heart surgery are exposed to high levels of circulating catecholamines. Our objective was to determine to what extent epinephrine (E)-related cardiotoxicity can be attributed to induced tachycardia. We assessed left ventricle function by pressure-volume data obtained by conductance catheter/micromanometer technique and correlated it with ultrastructure in newborn piglets (3 to 7 d old). Group A (n = 6) received E (1 p,g/kg/min) for 2 h, whereas group B piglets (n = 6) were atrially paced at a rate (220lmin) matched to group A. Left ventricle peak systolic pressure and stroke work were significantly higher @ < 0.05) in group A. End-systolic elastance increased during E infusion (70%) versus no significant change in group B. After 2 h of E infusion, end-systolic elastance was significantly reduced in group A from 9.8 + 3.5 to 5 + 2.4 mm HgImL ( p < 0.05).Chamber stiffness index increased during E infusion from 0.36 ? 0.2 to 0.6 + 0.3 mL-' ( p < 0.05) and remained High plasma levels of endogenous catecholamines exist in neonates having congenital heart disease (I), and administration of catecholamines is frequently required for hemodynamic support preoperatively. The inotropic effect of all p-agonists is mediated through activation of the enzyme adenylate cyclase, resulting in increased intracellular levels of CAMP and enhancement of transarcolemmal c a 2 + influx (2). The association between high circulating plasma catecholamines and acute cardiotoxicity has previously been studied (3, 4), and the mechanisms are attributed to impaired intracellular c a 2 + handling (5), reduced coronary blood flow, and formation of highly cytotoxic free radicals derived from catecholamine autoxidation (6). Because most p-agonists exert both positive inotropic and chronotropic effects, it is still unclear to what extent catecholamine-induced cardiomy- Supported by a grant from the Ontario Heart Foundation (T-1376).elevated (0.58 t 0.2 mL-') after E infusion was discontinued versus no change in group B. E-induced left ventricle dysfunction was associated with scattered but irreversible ultrastructural changes consisting of sarcolemmal rupture and loss of mitochondrial architecture, whereas only minor reversible changes such as microvesicular lipid accumulation and mitochondria1 swelling were seen in group B. We conclude that E cardiotoxicity in the neonate is independent of induced tachycardia. opathy is attributable to tachycardia. Therefore, this study was designed to compare the effects of rapid atrial pacing with those of E on LV function and ultrastructure in newborn piglets. Myocardial performance was assessed by the end-systolic and diastolic PV relationship (7) and correlated with ultrastructural and metabolic recovery by serial ATP measurements before and after administration of E and pacing.

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Section: Discussionsupporting

confidence: 61%

“…We used an open ence LV diastolic PV relation under physiologic condi- Table 3. Plasma E and NOR levels @glL) before, at 30 tions (19). However, the rationale for doing this was to obtain transmural ventricular biopsies on completion of the last function study.…”

Section: Discussionmentioning

confidence: 99%

Heart Rate Independence of Catecholamine-Induced Myocardial Damage in the Newborn Pig

et al. 1994

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“…The apparent improvement in chamber stiffness is not due to the improvement in active relaxation as measured by dP/dt min , as all three adrenergic agents improved active relaxation by this method, and neither DB nor EP improved RV chamber stiffness. In fact, there is evidence that administration of EP to the postbypass newborn piglet increases left ventricular chamber stiffness (28).…”

Section: Catecholamine Administrationmentioning

confidence: 99%

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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“…The validity of this technique for assessment of cardiac contractility has been established previously in adult animals 25 and has been adapted for analysis of newborn cardiac function by our group. 7 Recently, Applegate et al 26 have shown that the conductance catheter accurately measures absolute volumes at steady state but can underestimate the slope and position of the end-systolic PV relation when it is determined by caval occlusion. However, the end-systolic PV relation accurately measures the direction and magnitude of change in LV systolic function.…”

Section: = 16mmmentioning

confidence: 99%

Dose-related effects of magnesium on myocardial function in the neonate.

et al. 1994

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The antagonistic effects of magnesium ion as a calcium ion blocker may decrease calcium influx associated with ischemia. However, the effect of magnesium on the preischemic neonatal myocardium has not been investigated previously. The purpose of this study was to investigate the effects of the administration of increasing doses of magnesium on left ventricular performance in the neonate. We assessed left ventricular function (pressure-volume data obtained by the conductance catheter/micromanometer technique) in three groups (n=6 in each) of newborn pigs (3 to 5 days old) differing with respect to magnesium concentrations. Endsystolic elastance did not change during infusion in group A (magnesium=1.2 mmol/L), whereas in groups B (magnesium=8 mmol/L) and C (magnesium=16 mmol/L) it decreased significantly (P<.05) to 67±6% and 44±8% of baseline, respectively. The decrease in end-systolic elastance was associated with a significant reduction in cardiac output (P<.05) and stroke work (P<.05) in group C. After administration of magnesium, end-systolic elastance returned to baseline in group B in contrast to group C (78±3% of baseline value, P<.05). The slope constant of the end-diastolic pressure-volume relation decreased significantly (P<.05) from the preinfusion baseline values of 0.42±0.08 mL" 1 in group B and 0.46±0.05 mL" 1 in group C to 0.3±0.04 and 0.26±0.03 mL"', respectively, versus no change in group A. At the end of the experiment, the slope constant returned to baseline value in group B, whereas in group C it remained significantly lower (P<.05, 78±3% of baseline). We conclude that administration of 8 to 16 mmol/L magnesium affects the systolic function and alters the diastolic properties of the neonatal heart in a dose-response manner. can affect cardiac contractility and tension development by changing sarcolemmal and membrane binding of Ca 2 + , thus directly affecting resting membrane potentials and excitation-contraction coupling events.2 It is also now clear that small changes in free external Mg 2 + can exert significant effects on cardiac cell mechanical and electrical activities.3 Evidently, Mg 2 + can be considered as a natural Ca 2+ antagonist that may influence and control many cardiovascular functions.The effects of Mg 2 + on cardiovascular hemodynamics were studied mainly in adults.4 -5 However, the effects of Mg 2 + on cardiac mechanics in the intact neonatal or adult heart, using the pressure-volume (PV) relation, have not been studied. Therefore, this study was designed to examine the effects of the administration of varying doses of magnesium sulfate (MgSO 4 ) on left ventricular (LV) systolic and diastolic function in the neonate.

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Effects of high plasma epinephrine and Ca2+ concentration on newborn myocardial function following ischemia

Cited by 6 publications

References 0 publications

Heart Rate Independence of Catecholamine-Induced Myocardial Damage in the Newborn Pig

Heart Rate Independence of Catecholamine-Induced Myocardial Damage in the Newborn Pig

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

Dose-related effects of magnesium on myocardial function in the neonate.

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