Submitted on June 11, 2004
Accepted on November 17, 2004
Surfactant phospholipids and proteins are increased in fetal sheep with pulmonary hypertension secondary to fetal systemic arteriovenous fistula
Alexandra Benachi1, Jean-Marie Jouannic2, Anne-Marie Barlier-Mur3, Bernadette Chailley-Heu3, and Jacques R. Bourbon3*
1 INSERM U492, Faculte de Medecine-Universite Paris XII, Creteil, France; Matenite, Hopital Necker-Enfants Malades, AP-HP-Universite Paris V, Paris, France
2 Gynecologie-Obstetrique, Hopital Rothschild, AP-HP-Universite Paris VI, Paris, France
3 INSERM U492, Faculte de Medecine-Universite Paris XII, Creteil, France
* To whom correspondence should be addressed. E-mail: jacques.bourbon{at}creteil.inserm.fr.
To determine whether prenatal surfactant storage was altered in a model of systemic arteriovenous fistula (SAVF) with pulmonary hypertension, a fistula was created between the internal jugular vein and the carotid artery in 120-day fetal lambs, and surfactant material was
explored at 134 days. Total phospholipids (TPL) and di-saturated phosphatidylcholine (DSPC) were increased in whole lung tissue. Phospholipid analysis of isolated lamellar body fraction evidenced a specific increase of surfactant pool size: TPL and DSPC in this fraction
were enhanced 1.9 and 2.9 times, respectively, when referred to DNA. Although the steadystate level of transcripts of surfactant proteins SP-A and SP-B was not found to be changed at the time of sacrifice, semi-quantitative western blot analysis revealed elevated SP-A and SP-B protein contents 3- and 2-fold, respectively. These findings indicate markedly enhanced accumulation of surfactant material in the presence of surgically-induced prenatal pulmonary hypertension. Although total lung cell number was increased by 26%, SP-B immunolabeling
indicated that increased surfactant amount did not result from an increased alveolar type II cell proportion, but rather from an increased rate of storage. Whether similar changes in surfactant are encountered in human neonates with persistent pulmonary hypertension is worthy of investigation.
