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Inotropes in the hypoplastic left heart syndrome: effects in an animal model
C J Riordan1, F Randsbaek, J H Storey
1Division of Thoracic and Cardiovascular Surgery, University of Louisville School of Medicine, KY 40292, USA.
Insights
Different inotropic agents have varying effects on oxygen delivery in infants with hypoplastic left heart syndrome. Epinephrine improved oxygen delivery, while dobutamine decreased it, highlighting the need for careful drug selection in perioperative care.
Area of Science:
- Pediatric Cardiology
- Neonatal Physiology
- Pharmacology
Background:
- Hypoplastic left heart syndrome (HLHS) remains a critical congenital heart defect with high mortality.
- Effective perioperative care is crucial for improving outcomes in HLHS patients.
- Limited experimental data exist to guide pharmacologic therapy, particularly inotropic agents, for HLHS infants.
Purpose of the Study:
- To investigate the differential effects of commonly used inotropic agents on the ratio of pulmonary to systemic flow (Qp/Qs) and oxygen delivery in a neonatal model.
- To determine if inotropic agents are equally effective in increasing oxygen delivery in the context of altered hemodynamics.
Main Methods:
- A neonatal piglet model (n=6) was established with a shunt, atrial septal defect, and occluded right ventricular outflow to mimic HLHS physiology.
- High and low concentrations of dopamine, dobutamine, and epinephrine were administered.
- Hemodynamic parameters, including Qp/Qs and oxygen delivery, were measured.
Main Results:
- Dobutamine (15 µg/kg/min) increased Qp/Qs but decreased oxygen delivery (p<0.1).
- Epinephrine (0.1 µg/min) decreased Qp/Qs (p<0.05) and increased oxygen delivery (p<0.05), with improved systemic venous oxygen saturation.
- Dopamine showed a trend towards decreasing Qp/Qs and increasing oxygen delivery, but results were not statistically significant.
Conclusions:
- Inotropic agents like dopamine, dobutamine, and epinephrine have distinct effects on Qp/Qs and oxygen delivery in HLHS models.
- These differential effects, likely due to varying impacts on vascular resistance, suggest that not all inotropes are equally beneficial clinically.
- Systemic venous oxygen saturation and arteriovenous oxygen difference can serve as indicators to assess the efficacy of inotropes in improving oxygen delivery.
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.