Inotropes in the hypoplastic left heart syndrome: effects in an animal model.
BACKGROUND
Despite substantial changes in the surgical treatment of children born with the hypoplastic left heart syndrome, overall mortality remains high. Although further improvements in outcomes appear to depend on more effective perioperative care, few experimental data exist to guide appropriate pharmacologic therapy in these infants. Because different inotropic agents may have different effects on the ratio of pulmonary to systemic flow (Qp/Qs), we hypothesize that they may not be equally effective at increasing oxygen delivery.


METHODS
In neonatal piglets (n = 6; 3.5 to 6.5 kg), we placed an innominate artery-to-pulmonary artery shunt, created an atrial septal defect, and then occluded right ventricular outflow. We examined the effects of a number of commonly used inotropic agents, administering high and low concentrations of dopamine (5 and 15 micrograms.kg-1 .min-1), dobutamine (5 and 15 micrograms.kg-1.min-1), and epinephrine (0.05 and 0.1 microgram /min).


RESULTS
Dobutamine at 15 micrograms.kg-1.min-1 increased the Qp/Qs ratio from 1.03 +/- 0.6 at baseline to 2.52 +/- 0.55 (p < 0.05) and decreased oxygen delivery from 50 +/- 4.3 to 36 +/- 1.7 mL/min (p < 0.1). The arterial-venous oxygen difference increased as oxygen delivery went down, going from 44% +/- 1% to 48% +/- 2% (p < 0.1). Epinephrine at 0.1 microgram.kg-1.min-1 decreased the Qp/Qs ratio from 1.23 +/- 0.21 to 0.82 +/- 0.08 (p < 0.05) and increased oxygen delivery from 40 +/- 9.7 to 56 +/- 1.7 mL/min (p < 0.05). Systemic venous oxygen saturation increased from 36% +/- 4.8% to 50% +/- 8.6% (p < 0.05). Although dopamine decreased the Qp/Qs ratio and increased oxygen delivery, these changes were not statistically significant.


CONCLUSIONS
Dopamine, dobutamine, and epinephrine all increased cardiac output but had substantially different effects on the Qp/Qs ratio and on oxygen delivery, possibly due to differential effects on systemic and pulmonary vascular resistances. This suggests that inotropic agents may not be equally beneficial in the clinical setting. Systemic venous oxygen saturation and the arteriovenous oxygen difference may help determine if a given inotrope improves oxygen delivery.
Riordan
C J
CJ
Division of Thoracic and Cardiovascular Surgery, University of Louisville School of Medicine, KY 40292, USA.
Randsbaek
F
F
Storey
J H
JH
Montgomery
W D
WD
Santamore
W P
WP
Austin
E H
EH
D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use*; D004298:Dopamine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects*; D018636:Hypoplastic Left Heart Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D011300:Preoperative Care; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D004280:Dobutamine; D010100:Oxygen; D004298:Dopamine; D004837:Epinephrine