Effects of a Thromboxane A2 Analogue and Prostacyclin on Lung Fluid Balance in Newborn Lambs

We have previously shown that the pulmonary venoconstriction produced by a stable thromboxane A2 analogue (STA2) is attenuated by prostacyclin (PGI2), but PGI2 increases the STA2-induced edema. The present study was designed to determine the effects of STA2 and PGI2 on the fluid balance in isolated blood-perfused newborn lamb lungs. Vascular permeability was evaluated by use of the fluid flitration coefficient (Kf) and the osmotic reflection coefficient for total proteins (σ, hematocrit-protein double indicator technique), and pulmonary capillary pressure (Pc) was estimated by the double occlusion technique. All lungs had a period of hydrostatic stress induced by elevation of the left atrial pressure from 5 to 20 mm Hg to promote fluid filtration, and the rate of lung weight gain (ΔW/ΔT) during this period was determined. Studies were made in four groups; before the hydrostatic stress, lungs were given 1) STA2 (50 μg, n =6), 2) PGI2 (0.4 μg/kg/min, n =6), 3) both PGI2 and STA2 (n =6), or 4) vehicles (control, n =5). Measurements of Kf were made at the baseline period and after the hydrostatic stress. Kf was significantly increased by 76% with STA2, by 121% with PGI2, and by 157% with both PGI2 and STA2, but remained constant in controls. In comparison with control lungs, a similar ΔW/ΔT was observed with less of an increase in Pc during the hydrostatic stress in the STA2 group, and greater values of ΔW/ΔT were obtained with smaller elevations in Pc in the groups receiving PGI2 or both PGI2 and STA2. The σ 0.66 ± 0.07 in the control group was the highest in these experiments. Treatments with STA2 and/or PGI2 significantly decreased σ. These results suggest that both STA2 and PGI2 may increase pulmonary microvascular permeability to protein. Furthermore, PGI2 may increase fluid filtration by increasing vascular surface area.