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Pulmonary Transvascular Fluid Filtration and Microvascular Permeability to Plasma Proteins in Awake Newborn Lambs
Pulmonary Transvascular Fluid Filtration and Microvascular Permeability to Plasma Proteins in Awake Newborn Lambs* Richard D. Bland, MD., and Douglas D. McMiUan, M.D.
To improve our understanding of lung fluid and protein dynamics in the newborn lamb, we measured lung lymph flow and protein Bow, with simultaneous mean pulmonary arterial (Ppa) and left atrial (pr.;) pressures, in nine unanesthetized 7-14 day-old lambs. We prepared the lambs surgically by a modification of the method of Staub et al, I allowing at least two days for the lambs to recover from surgery before experiments began. Table 1 summarizes the results of 21 experiments in 9 Iambs and 22 previous experiments in 9 unanesthetized sheep." We did all studies during steady-state conditions for at least 2 hours. The results suggest there was a higher pulmonary transvaseular hydraulic pressure gradient in lambs than in sheep, causing greater filtration of fluid into the lung interstitium, with a small secondary increase in the bulk Bow of protein. The transvascular gradient for protein osmotic pressure was almost identical for the two groups of animals. Comparison of protein ratios helps to distinguish differences in fluid filtration from differences in membrane penneability. The concentration of albumin relative to globulin in both lymph and plasma was not significantly different in the two groups of animals. indicating that molecular sieving across the vascular endothelium did not differ appreciably in lambs and sheep. However. the total protein concentration in lymph relative to plasma was lower in the younger animals, consistent with a higher intravascular hydraulic pressure. In both lambs and sheep, the concentration of albumin in lymph relative to plasma was higher than that for total proteins, confirming the fact that irrespective of maturity, albumin traverses the vascular endothelium
Vascular Pressures pia Ppa
torr Lambs
Sheep
more readily than the larger globulin molecules. In 7 Iambs we measured the time for intravenouslyinjected ''''J-albumin to equilibrate in lymph at half the specific activity of plasma. We found that the protein tag equilibrated more rapidly (104 :+ 8 minutes) than it did in adult sheep (180 ::!: 20 minutes) previously studied by Vaughan and coworkers." Since the size of the sites for pulmonary transvasculur protein movement in lambs and sheep did not differ appreciably (suggested by almost identical albumin: globulin ratios), we conclude that the more rapid equilihration of 1::l5I~albumin in Iambs was the result of (1) higher pulmonary microvascular pressures. with increased lymph RO\\' and bulk protein Bow, and (2) more crosssectional area for transvascnlar protein exchange relative to the volume of distribution of the protein in the lung. Our data pertaining to protein transport suggest that either more pulmonary blood vessels participated in protein exchange or there were more sites for exchange per unit of vascular surface area in lambs than in sheep, Our results cannot differentiate those possibilities. At the end of a series of experiments in each animal, we measured extravascular lung water and dry bloodless lung weight by a modification- of the method of Pearce and associates." \Ve found that extravascular lung- water per unit of dry bloodless lung was greater in lambs (4,82 ±
.Il) than in sheep (4.45
±
.08). a result which is
consistent with Increased fluid filtration, produced by the greater transvascular hydraulic pressure gradient
in the lambs. REFERENCES
Protein Concentrations Lymph Plasma
Lymph
Flow
Protein Flow
g/lOO ml
Protein Hatios Lymph.Plasma Albumin .Olcbulin Total Proteins Albumin Lymph Plasma
mllhr·*
mg/hrt
2.96 ±.16
4.97 ±.II
.12 ±.02
,66
.95
±I
2 ±O.5
±.07
±,O4
.62 ±.02
±.O3
14 ±It
1
4.23 ±.13t
6.14
±OA
±.09t
.07 ±.Olt
.47 ±.08
1.01 ±.1O
.62 ±.04
± .Im
18
.;)\1
,fin
76 ±J)3 8~
±.02t
"Results represent average values ± the standard error of the average for 21 experiments in nine Iambs and 22 experiment- in nine sheep: "PPT gram of dry bloodless lung; tPeT gram of dry bloodless luna, per gram of plasma proteins: :f:8i~nifi('ant difference between lambs and sheep. P < .05, by unpaired t t-est
274
19TH ASPEN LUNG CONFERENCE
CHEST 71: 2, FEBRUARY, 1977 SUPPLEMENT
To improve our understanding of lung fluid and protein dynamics in the newborn lamb, we measured lung lymph flow and protein Bow, with simultaneous mean pulmonary arterial (Ppa) and left atrial (pr.;) pressures, in nine unanesthetized 7-14 day-old lambs. We prepared the lambs surgically by a modification of the method of Staub et al, I allowing at least two days for the lambs to recover from surgery before experiments began. Table 1 summarizes the results of 21 experiments in 9 Iambs and 22 previous experiments in 9 unanesthetized sheep." We did all studies during steady-state conditions for at least 2 hours. The results suggest there was a higher pulmonary transvaseular hydraulic pressure gradient in lambs than in sheep, causing greater filtration of fluid into the lung interstitium, with a small secondary increase in the bulk Bow of protein. The transvascular gradient for protein osmotic pressure was almost identical for the two groups of animals. Comparison of protein ratios helps to distinguish differences in fluid filtration from differences in membrane penneability. The concentration of albumin relative to globulin in both lymph and plasma was not significantly different in the two groups of animals. indicating that molecular sieving across the vascular endothelium did not differ appreciably in lambs and sheep. However. the total protein concentration in lymph relative to plasma was lower in the younger animals, consistent with a higher intravascular hydraulic pressure. In both lambs and sheep, the concentration of albumin in lymph relative to plasma was higher than that for total proteins, confirming the fact that irrespective of maturity, albumin traverses the vascular endothelium
Vascular Pressures pia Ppa
torr Lambs
Sheep
more readily than the larger globulin molecules. In 7 Iambs we measured the time for intravenouslyinjected ''''J-albumin to equilibrate in lymph at half the specific activity of plasma. We found that the protein tag equilibrated more rapidly (104 :+ 8 minutes) than it did in adult sheep (180 ::!: 20 minutes) previously studied by Vaughan and coworkers." Since the size of the sites for pulmonary transvasculur protein movement in lambs and sheep did not differ appreciably (suggested by almost identical albumin: globulin ratios), we conclude that the more rapid equilihration of 1::l5I~albumin in Iambs was the result of (1) higher pulmonary microvascular pressures. with increased lymph RO\\' and bulk protein Bow, and (2) more crosssectional area for transvascnlar protein exchange relative to the volume of distribution of the protein in the lung. Our data pertaining to protein transport suggest that either more pulmonary blood vessels participated in protein exchange or there were more sites for exchange per unit of vascular surface area in lambs than in sheep, Our results cannot differentiate those possibilities. At the end of a series of experiments in each animal, we measured extravascular lung water and dry bloodless lung weight by a modification- of the method of Pearce and associates." \Ve found that extravascular lung- water per unit of dry bloodless lung was greater in lambs (4,82 ±
.Il) than in sheep (4.45
±
.08). a result which is
consistent with Increased fluid filtration, produced by the greater transvascular hydraulic pressure gradient
in the lambs. REFERENCES
Protein Concentrations Lymph Plasma
Lymph
Flow
Protein Flow
g/lOO ml
Protein Hatios Lymph.Plasma Albumin .Olcbulin Total Proteins Albumin Lymph Plasma
mllhr·*
mg/hrt
2.96 ±.16
4.97 ±.II
.12 ±.02
,66
.95
±I
2 ±O.5
±.07
±,O4
.62 ±.02
±.O3
14 ±It
1
4.23 ±.13t
6.14
±OA
±.09t
.07 ±.Olt
.47 ±.08
1.01 ±.1O
.62 ±.04
± .Im
18
.;)\1
,fin
76 ±J)3 8~
±.02t
"Results represent average values ± the standard error of the average for 21 experiments in nine Iambs and 22 experiment- in nine sheep: "PPT gram of dry bloodless lung; tPeT gram of dry bloodless luna, per gram of plasma proteins: :f:8i~nifi('ant difference between lambs and sheep. P < .05, by unpaired t t-est
274
19TH ASPEN LUNG CONFERENCE
CHEST 71: 2, FEBRUARY, 1977 SUPPLEMENT