Surfactant decreases pulmonary vascular resistance and increases pulmonary blood flow in the fetal lamb model of congenital diaphragmatic hernia.
BACKGROUND
Experiments using animal models of neonatal respiratory distress syndrome have shown a decrease in pulmonary vascular resistance (PVR) with surfactant replacement, whereas studies with the lamb model of congenital diaphragmatic hernia (CDH) have demonstrated improvement in oxygenation and lung mechanics with this therapy. The aim of the present study was to measure the effects of surfactant replacement therapy on the pulmonary hemodynamics of the lamb model of CDH.


METHODS
Ten lambs with surgically created CDH and five control lambs were instrumented at term, with the placental circulation intact. Ultrasonic flow probes were positioned around the main pulmonary artery and the common origin of the left and right pulmonary arteries to record total lung and main pulmonary artery blood flow. Catheters were inserted to record systemic, pulmonary, and left atrial pressure. Five CDH animals received 50 mg/kg of surfactant by tracheal instillation just before delivery. All 15 animals were then ventilated for 4 hours.


RESULTS
Correcting the surfactant deficiency in the CDH lamb resulted in a significant increase in pulmonary blood flow, a decrease in PVR, and a reduction in right-to-left shunting. These improvements in hemodynamics were associated with a significant improvement in gas exchange over 4 hours.


CONCLUSIONS
The fetal lamb model of CDH has elevated PVR in comparison to controls. Prophylactic surfactant therapy reduces this resistance and dramatically increases pulmonary blood flow while reducing extrapulmonary shunt. A surfactant deficiency may be partially responsible for the persistent pulmonary hypertension in neonates with CDH.
O'Toole
S J
SJ
Buffalo Institute of Fetal Therapy (BIFT), Children's Hospital of Buffalo, NY 14222, USA.
Karamanoukian
H L
HL
Morin
F C
FC
Holm
B A
BA
Egan
E A
EA
Azizkhan
R G
RG
Glick
P L
PL
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006548:Hernia, Diaphragmatic / Q000473:pathology / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D011663:Pulmonary Surfactants