Passage of macromolecules between alveolar and interstitial spaces in foetal and newly ventilated lungs of the lamb.

1. Experiments were performed on exteriorized foetal lambs to measure transfer of macromolecules (proteins and [(125)I]PVP) between lung alveolar liquid (A(l)) and lung interstitial liquid as represented by lung lymph (L(ly)). Transfer was measured in the foetus and during a 2 hr period of positive pressure ventilation.2. In thirteen experiments [(125)I]PVP was introduced into A(l) and, after a control period, the lungs were ventilated for 2 hr. In six other experiments the [(125)I]PVP was injected intravenously; and in two of these the lungs were ventilated for 2 hr. Measurements were made of protein and of [(125)I]PVP concentration in plasma and L(ly) collected at intervals throughout the experiment, as well as in A(l) obtained before ventilation and at the end of ventilation after degassing the lung. [(125)I]PVP in the samples was separated into fractions of different Stokes-Einstein radius by gel filtration using Sephadex G-200.3. Before ventilation there was evidence of a negligible transfer of protein from L(ly) to A(l) (mean protein A(l)/L(ly) = 0.014) or of [(125)I]PVP from A(l) to L(ly) (mean [(125)I]PVP L(ly)/A(l) = 0.00017). The effect of ventilation for 2 hr was to produce an increase in both ratios, but by a variable amount (after 2 hr ventilation mean protein A(l)/L(ly) = 0.70 +/- 0.08 (S.E. of mean) and mean [(125)I]PVP L(ly)/A(l) = 0.48 +/- 0.09). By calculating L(ly)/A(l) ratios for [(125)I]PVP fractions obtained by gel filtration it was shown that in transfer from A(l) to L(ly) during ventilation molecular sieving could be detected, the degree of which was expressed by means of a Relative Sieving Index (RSI). Significant correlations were found between the minimum surface tension of lung extracts, and two other indicators of lung maturity on the one hand, and the protein and [(125)I]PVP ratios and RSI on the other; so that the more mature the lamb the less the transfer of macromolecules during ventilation and the greater the degree of molecular sieving.4. By comparing concentrations of [(125)I]PVP gel filtration fractions in lymph and plasma, when the [(125)I]PVP had been placed in A(l), we demonstrated some sieving of molecules (in the range 34-15 A) in their absorption from interstitial space to plasma.5. It was concluded that in the lungs of the foetal lamb there is an almost complete barrier to the transfer of macromolecules between alveolar and interstitial spaces; that positive pressure ventilation for 2 hr causes a very variable degree of break-down in this barrier, and that the degree of break-down is usually greater in immature than in mature lungs.