Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
Pediatric Critical Care Medicine www.pccmjournal.org 1
Objectives: To investigate the effect of right ventricular stunning on
interventricular relationships in newborn piglets and to determine
the effect of three commonly used inotropic treatment strategies.
Design: Randomized, placebo-controlled animal study.
Setting: Aarhus University Hospital, animal laboratory.
Subjects: Twenty-eight newborn (4-d old) farm-bred piglets.
Interventions: Acute right ventricular failure was induced by 10
cycles of alternating 3 minutes of ischemia and reperfusion of the
right coronary artery. After right ventricular failure was induced,
treatment with epinephrine + milrinone, dopamine + milrinone,
dobutamine, or control (saline) was initiated, and the animals were
observed for 180 minutes.
Measurements and Main Results: Right and left ventricular
systolic and diastolic variables were measured using pressure-
volume loops recorded by conductance catheters. Arterial and
central venous pressures were recorded, and cardiac index
was determined by placing a flow probe around the pulmonary
artery. Whole-body perfusion was evaluated by measuring pH
and lactate in arterial blood samples. Induction of right ventricu-
lar stunning resulted in decreased ejection fraction (51% ± 4%
vs 40% ± 12%, p = 0.0004); caused an interventricular sep-
tum deviation, decreased mean arterial pressure (49 ± 10 mm
Hg vs 43 ± 11 mm Hg, p = 0.03), and increased blood lactate
(1.85 ± 0.6 mM vs 5.79 ± 3.16 mM, p < 0.00001); and led to a
decrease in blood pH (7.37 ± 0.08 vs 7.23 ± 0.13, p < 0.00001).
A mortality rate greater than 50% was observed in the control
group. All inotropic interventions increased contractility signifi-
cantly in both the left and right ventricle. The effect of dobu-
tamine on right ventricular failure decreased after 30 minutes
and was indistinguishable from the control group after 3 hours.
Dobutamine-treated animals had lower perfusion pressures and
blood pH compared with epinephrine + milrinone and dopa-
mine + milrinone groups.
Conclusions: In newborn piglets, dobutamine had a nonsustained
effect on right ventricular failure, resulting in decreased contrac-
tility and impaired perfusion compared with both dopamine and
epinephrine administered in combination with milrinone. (Pediatr
Crit Care Med 2014; XX:00–00)
Key Words: adrenaline; animal model; cardiovascular agents;
catecholamine; dobutamine; dopamine; heart failure; milrinone;
myocardial stunning; neonate; newborn; nonsustained; right
heart; right heart failure; right ventricle; stunning
L
ow cardiac output (CO) is observed in approximately
25% of all children undergoing cardiac surgery for con-
genital heart disease (1, 2) and may be related to left or
right ventricular (RV) failure. RV failure is more common in the
pediatric population than in the adult population and is associ-
ated with systemic hypotension and decreased coronary perfu-
sion, which may further aggravate ventricular performance.
Indications for the use of epinephrine, dopamine, dobu-
tamine, and milrinone are well described for the treatment
of acute heart failure in adults. However, evidence for the
choice of therapy in acute heart failure in children, espe-
cially neonates, is limited (3). A comparison of the effect of
Copyright © 2014 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0000000000000202
1
Department of Anaesthesiology and Intensive Care, Aarhus University
Hospital, Aarhus, Denmark.
2
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
3
Department of Cardiothoracic and Vascular Surgery, Aarhus University
Hospital, Aarhus, Denmark.
4
The Heart Centre, Division of Cardiology, The Hospital for Sick Children,
Toronto, ON, Canada.
5
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Supported, in part, by The Danish Council for Independent Research,
Medical Sciences; Danish Children Heart Foundation; Foreningen
Østifterne; and Department of Clinical Medicine, Aarhus University.
The authors have disclosed that they do not have any potential conflicts
of interest.
Address requests for reprints to: Hanne B. Ravn, DMSc, Department of
Anaesthesiology and Intensive Care, Aarhus University Hospital, Skejby,
Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. E-mail: hbr@ki.au.dk
For information regarding this article, E-mail: janus.hyldebrandt@ki.au.dk
Inotropic Therapy for Right Ventricular Failure
in Newborn Piglets: Effect on Contractility,
Hemodynamics, and Interventricular Interaction
Janus A. Hyldebrandt, MD
1,2
; Christian A. Frederiksen, MD
1
; Johan Heiberg, MD
3
;
Susani Rothmann, MD
3
; Andrew N. Redington, FRCP
4
; Michael R. Schmidt, PhD
5
;
Hanne B. Ravn, DMSc
1