The Effects of in Vivo Pulmonary Oxygenation on Lung Liquid Production in Near‐Term Fetal Sheep

Abstract

Lung liquid (LL) is secreted into the fetal lung lumen, but it must be rapidly absorbed at birth to allow air breathing. In vitro studies have implicated oxygen as a possible factor causing the switch from secretion to absorption of lung liquid at birth. We developed a technique of oxygenating the fetal lung using liquid ventilation with haemoglobin (Hb) solutions in chronically catheterized fetal lambs (129-140 days gestation; term, 147 days). In some experiments 2,3-diphosphoglycerate (DPG) was added to increase oxygen delivery. LL secretion rate (Jv) was measured using an indicator dilution method. Eighteen fetuses were divided into four groups and ventilated with liquid under the following conditions: (i) Hb with oxygen, (ii) Hb without oxygen, (iii) Hb with DPG and oxygen and (iv) Hb and DPG without oxygen. There was a significant rise (2.6 mmHg, P < 0.02) in fetal arterial Po2 in group iii, but in none of the other groups. In the first 3 h of liquid ventilation there was no difference in Jv between the groups. In group i, during hours 4-6 of liquid ventilation, there was a significant rise in secretion rate from 2.25 +/- 0.88 to 3.74 +/- 0.85 ml h-1 kg-1 (P < 0.001). In group iii, when comparing Jv in the first 3 h of liquid ventilation with that in the following 3 h period of liquid ventilation, a strong trend towards reduction in secretion was observed, falling from 3.03 +/- 0.65 to 0.74 +/- 0.92 ml h-1 kg-1 (three of the four experiments showed a significant decrease in Jv in hours 4-6). These experiments indicate that oxygen delivered to the fetus using liquid ventilation with haemoglobin solutions leads to increased LL secretion when oxygen delivery is small, and suggest there is a decrease in secretion with greater oxygen delivery to the lung.