CHANGES IN LUNG LIQUID DURING SPONTANEOUS LABOR IN FETAL SHEEP

The goals of this study were 1) to examine changes in lung liquid formation and composition during spontaneous labor in fetal lambs and 2) to determine the importance of beta-adrenergic stimulation and transepithelial Na+ flux in removing liquid from the lung lumen near birth. We measured net production of lung liquid (J(v)), lung liquid composition, and transpulmonary electrical potential difference (PD) before and during labor in fetal sheep with chronically implanted tracheal and vascular catheters. We determined J(v) by measuring rate of change in lung liquid concentration of I-125-albumin, an impermeant tracer that was mixed in lung liquid at the start of each study. In 17 paired experiments, J(v) decreased from 11 +/- 2 ml/h (J(v) > 0 = secretion) before labor to -1 +/- 2 ml/h (J(v) < 0 = absorption) during labor; in 5 paired experiments, PD changed from -7 +/- 1 mV (lumen negative) before labor to -12 +/- 1 mV during labor. To determine whether absorption of lung liquid during labor is the result of beta-adrenergic stimulation, we studied the effect of propranolol on J(v) during labor. When propranolol (40 mu M) was added to lung liquid during active labor, J(v) decreased from -2 +/- 2 to -8 +/- 3 ml/h (n = 9). Thus, propranolol did not inhibit lung liquid absorption during labor. To determine whether transepithelial Na+ movement provides the driving force for lung liquid clearance during labor, we tested the effects of amiloride, an Na+ transport inhibitor, on J(v) and PD. When amiloride (100 mu M) was mixed in lung liquid during labor, J(v) increased from 0 +/- 2 to 9 +/- 3 ml/h (n = 7) and PD changed from -7 +/- 1 to -2 +/- 1 mV (n = 4). These findings indicate that spontaneous labor is associated with a reduction in rate of formation of lung liquid in fetal sheep, often resulting in net liquid absorption. This decrease or reversal of lung liquid flow is driven by Na+ flux out of lung lumen and does not require mu-adrenergic stimulation.