Permeability of lung capillaries to macromolecules in foetal and new‐born lambs and sheep

Abstract

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.

Increased Sheep Lung Vascular Permeability Caused by Pseudomonas Bacteremia

“…The role of lung lymphatics in protecting against pulmonary edema has been suggested (19,20,30), but not generally appreciated (31). Our studies show that lung lymphatics in awake sheep have the capacity to clear large quantities of filtered fluid (up to 85 ml/h in animal S36-72) and protein.…”

“…The ratios of extravascular lung water to dry weight of bloodless lung (Qwl/dQl) are listed in Table IV (18,19).…”

Lung Fluid Dynamics in Awake Newborn Lambs

“…To achieve these differences in the presence of the aforementioned pore radii, Boyd et Finally, we must explain why other investigators have found a three-to fourfold difference in lymph flow between lambs and sheep in acute experiments (2)(3)(4), compared with the 57% difference we are reporting. Although there was an eightfold difference in body weight between lambs and sheep, the lung tissue of the lambs was only one-fourth the mass of lung tissue of the sheep.…”

“…Boyd et al (4) reported that the concentration of both albumin and globulin in lymph relative to plasma was greater in newborn than in older sheep. They did not measure pulmonary vascular pressures.…”

“…Based on their data, these investigators derived a pulmonary microvascular pore radius of 90A for lambs, compared with 130 A for older sheep; they calculated the pore area per unit path length of pulmonary capillaries in lambs to be 16Y2 times greater than that in sheep (4). To achieve these differences in the presence of the aforementioned pore radii, Boyd et Finally, we must explain why other investigators have found a three-to fourfold difference in lymph flow between lambs and sheep in acute experiments (2)(3)(4), compared with the 57% difference we are reporting.…”