SUMMARY1. Two sets of experiments were performed on intact foetal lambs exteriorized at Caesarean section; in one set radioactively labelled test substances (inulin, sucrose, mannitol, erythritol, urea) were injected I.V. either singly or in pairs and then followed in plasma, lung lymph and alveolar liquid; in the other set labelled test substances (inulin, sucrose, mannitol, erythritol, D-serine, L-serine, D-a-alanine, urea, water, thiourea, N-ethylthiourea) were introduced singly, in pairs, or sequentially into alveolar liquid and their concentration followed in alveolar liquid and plasma.2. Inulin was found to cross lung capillary walls but not alveolar walls. Measurements of its concentration following injection into alveolar liquid were used to determine the volume of foetal alveolar liquid (mean = 30 ml./kg) and its rate of formation (mean = 0-036 ml./min. kg). The volume of the lung interstitial space was determined from previous experiments in which [1251]PVP had been injected I.v. then measured after 2 hr in lung tissue and lung lymph (mean = 10 4 % foetal lung weight after withdrawal of liquid; . 20 % wet lung tissue weight).3. Transfer constants (min-') for lung capillaries (Kc) and alveoli (KO) were obtained from the experimental results by compartmental analysis. Permeability constants (PC and Po, cm/sec) were derived from them using estimates for capillary and alveolar areas. For lipid insoluble molecules Pc and PO both increased with decreasing molecular radius, the effect being much greater for PO than Pc. Po was also shown to increase with lipid solubility of the test molecule even though molecular size increased with lipid solubility in the series tested (urea, thiourea, N-ethylthiourea).
1. Lymph from the lungs of lambs and sheep was found to enter both the right lymph duct and the thoracic duct. Right lymph duct flow was collected by constructing a venous sac, the venous tributaries of which were ligated but which the right lymph duct entered; thoracic duct flow was collected by cannulating the duct. Lymph from sites other than the lungs was excluded from the collections.2. Measurements were made of the surface tension characteristics of lung extracts and of the liquid present in foetal lungs. These values were used together with gestational age and crown-rump length to designate the foetal lambs into mature and immature groups.3. Lymph flow from the lungs averaged 0.99 ml./kg body wt./hr in immature foetal lambs, and 1.81 ml./kg/hr in mature foetal lambs before the start of ventilation. Lymph flow from the lungs of spontaneously delivered new-born lambs (mean age 51 hr) averaged 0.86 ml./kg/hr. In adult ewes right lymph duct flow averaged 0.11 ml./kg/hr and total lung lymph flow was estimated indirectly to be 0.33 ml./kg/hr. Calculated rates of protein flow in lung lymph (flow x protein concentration) were greater in foetal lambs than in adult sheep.4. Total thoracic duct flow averaged 2.48 ml./kg/hr in immature foetal lambs, 5.30 ml./kg/hr in mature foetal lambs, 3.65 ml./kg/hr in new-born lambs, and 2.92 ml./kg/hr in adult ewes.5. At the start of ventilation there was an increase in lymph flow from the lungs, which at 15-30 min reached a mean of 6.4 ml./kg/hr in mature lambs and 2.6 ml./kg/hr in immature lambs. At the same time the protein concentration of lymph decreased but the calculated protein flow increased.6. The lungs of foetal lambs weighed more than the lungs of spontaneously delivered new-born lambs, and the difference could be accounted for by liquid which could be aspirated through the trachea of the foetal lamb. On ventilation of the lungs for 2 hr, without first allowing the escape of any lung liquid, lung weight measurements indicated that about 66% of the lung liquid had been taken up in mature lambs and about 50% in immature lambs.7. It was concluded that the rate at which lymph is formed in the lungs is greater per kilogram body weight in foetal than in new-born lambs and greater in them than in ewes. The increase in lymph flow at the start of ventilation could account for the removal of about 40% of the liquid present in the lungs of the mature foetus and about 25% of the liquid in the lungs of the immature foetus.
SUMMARY During the 10 years [1966][1967][1968][1969][1970][1971][1972][1973][1974][1975] 148
SUMMARY1. The permeability of lung capillaries to macromolecules was investigated in immature and mature foetal lambs, new-born lambs and young sheep. The placental circulation of the foetal animals was maintained intact after delivery by Caesarian section. New-born lambs and sheep were mechanically ventilated. Samples of plasma and lymph that had drained from the lung via the thoracic duct were collected over a period of 1-5 hr.2. The proteins in plasma and lymph samples were separated by fractionation on columns of Sephadex G-200. Plasma yielded three peaks of protein concentration. The Kav value of each peak was determined, and, by calibrating the columns with known proteins, the mean radius of equivalent sphere (a) of the proteins in peak I was shown to be similar to that of fibrinogen > 110 A, peak II to y-globulin -54 A and peak III to albumin -34 A. Lung lymph contained the same three constituent peaks as plasma but in lower concentration. In all four groups mean lymph/plasma concentration (L/P) ratio was significantly different for each of the three peaks, being lowest for the largest molecules (peak I) and highest for the smallest (peak III).3. In five mature foetal lambs polydisperse polyvinylpyrrolidone labelled with 1251 ([1251]PVP) was injected i.v. early in the experiment: count rates in fractionated samples showed for plasma a continuous decline with time after injection, and for lung lymph an increase to a maximum then a decline. Steady-state L/P ratios for eleven fractions of PVP of differing molecular size ranging from 110 to 17 A were derived by compartmental analysis. For a given molecular size PVP L/P ratios were similar to protein L/P values.4. The regression of PVP L/P ratio on Kav was linear (correlation R. D. H. BOYD AND OTHERS coefficient r = 0.99), and the slope of the regression of protein L/P ratio on Kay was significantly steeper for new-born lambs than for mature foetuses (P < 0 025) and sheep (P < 0.005), and steeper for immature foetuses than sheep (P < 0 01).5. PVP and protein L/P ratios (mature foetuses) plotted against a showed a sigmoid relation with agreement between the two sets of L/P ratios. The goodness of fit between our experimental results and Landis & Pappenheimer's (1963) capillary pore theory (eqn. (1)) was examined: L/P ratios for the larger molecules ( > 75 A) appeared to be too high. By recalculating ratios on the assumption that the largest molecules (110 A) escape unrestricted from the capillary via leaks, the discrepancy disappears.6. Values for pore radius (r), and pore area per unit path length (A/Ax) have been calculated for each of the four groups; r ranged from 90 to 150A, A/Ax from 3-3 to 0-2 cm x 103.kg-'. In new-born lambs the value of r was significantly smaller, and A/Ax larger than that of any other group. The inferences to be drawn from these results are discussed.
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