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

Abstract

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 ...

Dobutamine in Paediatric Population: A Systematic Review in Juvenile Animal Models

“…For example, in a pulmonary hypertension model, dobutamine decreased the pulmonary artery pressure and pulmonary vascular resistance at 5 and 10 µg/kg/min [20]. In a neonatal piglet model of hypoplastic left heart syndrome an increase in the Qp/Qs ratio was observed, possibly due to differential effects on systemic and pulmonary vascular resistance [10], and in a model of right ventricular injury in young swine indices of pulmonary vascular impedance were found to decrease [14].…”

“…In this regard, most authors agree that dobutamine infusion improves cardiac output mainly at doses higher than 10 µg/kg/min [6], [8]–[14], [16]–[19]. It seems that at short term infusion this improvement was mainly due to an increase in heart rate [9], [11], [12], [16], [18], whereas at long term the increment in stroke volume is more prevalent [6], [8], [9], [17].…”

“…Only one of the studies included was blinded [6], while randomization was reported in 42% of the studies [6]–[9], [11], [13], [14], [16], [17], [20]. Similarly, 42% of the studies used a control group [5]–[8], [12], [13], [15], [17], [21], [22].…”

Neurohormones as markers of right- and left-sided cardiac dimensions and function in patients with untreated chronic heart failure

“…We have no obvious explanation for why adrenaline is increased in patients with increased right ventricular dimensions. However, adrenaline has been demonstrated to be beneficial in cases of isolated right ventricular injury [26].…”

Assessment of the right ventricle in donation after circulatory death hearts

“…20 Furthermore, epinephrine showed a larger increase in PA flow relative to the increase in RV total hydraulic power than dobutamine. 20 These findings can be explained by the fact that epinephrine decreases the myocardial oxygen demand in the RV and increases the cardiac output most efficiently compared to dobutamine and norepinephrine because of its vasodilatory contribution to the PA as well as its energetic efficiency on the RV. By reducing the afterload of the RV in the DCD heart using the appropriate catecholamine agent, myocardial salvage may increase and subsequently prevent remodeling and failure in the acute phase of posttransplantation.…”