Fetal model of single ventricle physiology: hemodynamic effects of oxygen, nitric oxide, carbon dioxide, and hypoxia in the early postnatal period.
BACKGROUND
In patients with single ventricle physiology, the distribution of flow to the systemic and pulmonary circulations, which are in parallel, largely depends on the relative resistances in the respective vascular beds. Although neonatal palliation in patients with single ventricle physiology has become more common, medical management during the perinatal and perioperative periods is often based primarily on personal and institutional experience and is complicated by the transition to postnatal life and the effects of cardiopulmonary bypass. The lack of an animal model that suitably mimics single ventricle physiology has impeded progress in this area.


OBJECTIVE
The purpose of the current study was to investigate the effects of respiratory manipulations on pulmonary hemodynamics in the early neonatal period in a reproducible model of single ventricle physiology created in utero.


METHODS
A 10 mm Damus-Kaye-Stansel aortopulmonary anastomosis was created in fetal sheep (n = 14) at 140 +/- 1.2 days' gestation, with pulmonary blood flow provided through a 5 mm aortopulmonary shunt after ligation of the main pulmonary artery distally. Two to 3 days after delivery at term, lambs (n = 11) underwent an open sternotomy and 30 minutes of deep hypothermic circulatory arrest. Both before and after bypass, respiratory manipulations, including administration of nitric oxide (80 ppm), 100% oxygen, 10% oxygen, and 5% carbon dioxide, were performed and hemodynamic variables were measured.


RESULTS
Nitric oxide and oxygen caused a decrease in pulmonary vascular resistance and an increase in the pulmonary/systemic blood flow ratio, both before and after bypass. Hypoxia and carbon dioxide produced a significant rise in pulmonary vascular resistance and a significant drop in the ratio of pulmonary to systemic blood flow.


CONCLUSIONS
Oxygen, nitric oxide, and carbon dioxide all appear to be useful means of manipulating pulmonary vascular resistance and pulmonary/systemic blood flow ratio in neonatal lambs with single ventricle physiology, but further investigation is necessary to understand their dose responsive effects and the effects of prolonged administration.
Reddy
V M
VM
Division of Cardiothoracic Surgery, University of California San Francisco, USA.
Liddicoat
J R
JR
Fineman
J R
JR
McElhinney
D B
DB
Klein
J R
JR
Hanley
F L
FL
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006324:Heart Arrest, Induced; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006352:Heart Ventricles / Q000002:abnormalities; D006439:Hemodynamics; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D009569:Nitric Oxide / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects; D015203:Reproducibility of Results; D012756:Sheep; D013249:Sternum / Q000601:surgery; D013908:Thoracotomy; D014655:Vascular Resistance / Q000187:drug effects
D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen