The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis

The purpose of the present study was to determine if pulmonary prostacyclin synthesis was stimulated by spontaneous onset of breathing by unanesthetized fetuses at birth. Cannulae were implanted and flow cuffs placed in fetal lambs and goats (0.93 term). Fetuses were delivered by cesarean section at 0.95 term and began breathing spontaneously. Prostacyclin in blood was determined by radioimmunoassay of its hydrolysis product, 6–ketoprostaglandin F_1α using methods that produced the same values in duplicate samples as did gas chromatography with electron capture detection. Fetal pulmonary prostacyclin production (left lung) [(left pulmonary venous concentration — pulmonary arterial concentration) × left pulmonary blood flow] was undetectable [−1.7 ± 1.0 (SEM) ng PGI_2·kg⁻¹ ·min⁻¹] and fetal pulmonary vascular resistance (left lung) high (5.1 ± 0.9 mm Hg · kg·min · ml⁻¹). Pulmonary prostacyclin production increased to 30.1 ± 12.3 ngPGI₂ · kg ⁻¹ · min ⁻¹ and pulmonary vascular resistance declined to 0.5 ± 0.1 mm Hg · kg · min · ml⁻¹ 15 min after–birth. Pulmonary vascular resistance remained low even though pulmonary prostacyclin production fell 2–5 h after birth. These results, coupled with earlier studies using indomethacin to inhibit prostaglandin synthesis, support the hypothesis that pulmonary prostacyclin synthesis participates in the decline of pulmonary vascular resistance that accompanies the onset of ventilation at birth, but may be less important in maintenance of low pulmonary vascular resistance once reduced pulmonary vascular tone has been established.