Estimation of lung liquid production in fetal sheep with blue dye dextran and radioiodinated serum albumin

Lung liquid production and reabsorption rates and lung volumes were measured in 99 fetal sheep (119-148 days of gestation) by indicator-dilution methods with the simultaneous use of blue dye dextran (BDD) and radioiodinated serum albumin (RISA). There were no significant differences between rates of lung liquid production or reabsorption by the two methods (n = 71 pairs; paired t-test; Wilcoxon test; ANOVA); this was equally true for rates in milliliters per hour or milliliters per kilogram body weight per hour and was independent of age. Volumes measured by both methods showed a close linear relationship (r = 0.97; for slope P < 0.0001; n = 99), whether expressed as milliliters or milliliters per kilogram body weight. Either method could give the higher volume. Values differed by only approximately 4%, independent of age or parameter (ml or ml/kg body wt; volumes regressed to original volume, or as measured in untreated control hours). However, this small difference was significant by paired t-test or Wilcoxon test when all data were combined irrespective of age; it was not significant after allowance for gestational age (two-way ANOVA). Both indicators showed the same increase in lung volume toward birth and the same fall when related to body weight (slopes significant P = 0.0003-0.0004; r = 0.93). Two-way ANOVA showed that the declines were significant (P = 0.003). The data suggest that 1) there was no significant difference in production or reabsorption rates measured by BDD or RISA, 2) differences in volumes measured by the two indicators were only significant if gestational age was ignored and were too small to have physiological importance, and 3) although BDD and RISA each may have methodological weaknesses, for purposes of measuring lung liquid volumes both are sufficiently accurate and reproducible to obtain meaningful physiological results.