Vasopressin Effects On Lung Liquid Volume In Fetal Sheep

The normal switch from placental to pulmonary gas exchange at birth requires rapid removal of liquid from the lungs. Previous reports contend that vasopressin may be important in regulating this process, but this notion derives from studies in which fetal sheep received very large doses of vasopressin that yielded plasma concentrations at least 10 times greater than those that have been measured during normal labor. To study the physiologic effects of vasopressin on lung liquid volume in fetal sheep, we made three sets of experiments. First, we measured plasma vasopressin concentrations [VP] in 15 late-gestation fetal sheep, five of which were at various stages of spontaneous labor. [VP] in these fetuses ranged from <1 (prelabor) to 31 (during labor) mu U/mL; postmortem extravascular lung water (EVLW) ranged from 4.5 to 14.5 g/g dry lung tissue. in a second series of studies, we measured EVLW in five sets of near-term (138 +/- 1 d, term = 147 d) twin fetal sheep that received an 8-h i.v. infusion of either isotonic saline (control twin) or AVP (AVP-treated twin) at a rate of similar to 1 (mU/kg)/min. This dose was chosen to mimic [VP] measured in fetuses that had been studied during labor. [VP] did not change in the control twins, whereas [VP] increased from 1.8 +/- 1.0 to 27.7 +/- 3.5 mu U/mL in treated twins. There was a small, statistically significant difference in EVLW between twins that received AW and untreated twins (11.9 +/- 1.8 versus 14.6 +/- 2.8 g/g dry lung). in a third series of studies, we measured net production of lung liquid (Jv) by an indicator dilution technique in 16 fetal sheep that received an i.v. infusion of isotonic saline for 2 h followed by AVP for up to 8 h. [VP] averaged 23.4 +/- 6.5 mu U/mL during AVP infusion. For six fetuses that were studied at <132 d (128 +/- 4 d) gestation, Jv did not change during AVP infusion (11.1 +/- 6.7 mL/h versus control, 10.2 +/- 4.7 mL/h); for 10 fetuses >132 d (135 +/- 2 d) gestation, Jv decreased from 11.3 4.7 mL/h during the control period to 8.6 +/- 5.4 mL/h during AVP infusion. Net secretion of lung liquid did not switch to net absorption in any of the 16 fetuses that received AVP. Thus, i.v. infusion of AVP, at a rate designed to mimic [VP] measured during spontaneous labor, led to modest reductions in Jv and EVLW, but did not cause net absorption of lung liquid in late-gestation fetal sheep.