Fibronectin deficiency and intestinal transvascular fluid balance during bacteremia

1982 ◽  
Vol 242 (4) ◽  
pp. H557-H564
Author(s):  
B. C. Dillon ◽  
T. M. Saba

Reticuloendothelial (RE) clearance dysfunction, which can be induced by opsonic fibronectin deficiency, has been correlated with organ failure during sepsis. We investigate the role of opsonic fibronectin deficiency and RE blockade in modulating alterations in intestinal transvascular fluid balance induced by Pseudomonas bacteremia using an isolated, innervated, and autoperfused canine small intestinal segment. Intravenous infusion of gelatin-coated particles was used to induce fibronectin deficiency and RE blockade. Lymph flow and lymph/plasma (L/P) protein concentration ratios were stable following intravenous challenge with bacteria or gelatin-coated particles. In contrast, lymph flow increased and L/P ratio decreased significantly when bacteremia coexisted with particle-induced opsonic fibronectin deficiency and RE blockade. This elevation in lymph flow and decline in L/P ratio was associated with normal vascular permeability to albumin, IgG, and IgM. The increase in intestinal fluid flux during bacteremia with RE blockade appears to be due to an increase in microvascular hydrostatic pressure and not to an increase in vascular permeability. These findings emphasize a potentially important role for fibronectin and associated RE system function as determinants of fluid filtration during sepsis.

2005 ◽  
Vol 99 (2) ◽  
pp. 556-563 ◽  
Author(s):  
David B. Pearse ◽  
Robert M. Searcy ◽  
Wayne Mitzner ◽  
Solbert Permutt ◽  
J. T. Sylvester

Ventilation (V̇) increases lung lymph flow (Q̇l), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V̇-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min−1, results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min−1 and compared with f = 10 min−1. Three additional groups of six sheep were perfused for 100 min with control V̇ (10 ml/kg, 10 min−1). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Q̇l and vice versa, without corresponding effects on the rate of edema formation. For the same change in V̇, changing Vt had a greater effect on Q̇l than changing f. The change in Q̇l caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Q̇l caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V̇ altered Q̇l through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V̇-induced changes in fluid filtration.


1980 ◽  
Vol 49 (3) ◽  
pp. 516-520 ◽  
Author(s):  
K. L. Brigham ◽  
S. J. Padove ◽  
D. Bryant ◽  
C. R. McKeen ◽  
R. E. Bowers

Because, in sheep, histamine-induced increased lung vascular permeability is prevented by diphenhydramine, we tested the effects of diphenhydramine on the sheep lung vascular response to endotoxin. We infused E. coli endotoxin (0.40-1.00 micrograms/kg) with and without diphenhydramine (3.0 mg/kg bolus + 1.5 mg . kg-1 . h-1) in the same unanesthetized sheep while measuring pulmonary arterial (Ppa) and left atrial (Pla) pressures, lung lymph flow (Qlym) and lymph (L) and plasma (P) protein concentrations. Endotoxin caused pulmonary hypertension soon after infusion (base-line Ppa = 22 +/- 3 (SE) cmH2O; after endotoxin Ppa = 40 +/- 2; P less than 0.05, n = 6) and after several hours an increase in permeability reflected in high flow of protein-rich lymph (base-line; Qlym = 7.5 +/- 1.4 (SE) ml/h, L/P protein concentration = 0.60 +/- 0.02: after endotoxin; Qlym = 21.4 +/- 3.1, P less than 0.05; L/P = 0.66 +/- 0.03, P less than 0.05). In the presence of diphenhydramine, endotoxin caused identical pressure changes but Qlym was lower during the period of increased permeability (16.7 +/- 3.0 (SE) ml/h, P less than 0.05 compared to endotoxin alone) and L/P protein concentration was similar (0.68 +/- 0.04, P = NS). We conclude that endogenous histamine may be partly responsible for the increase in lung vascular permeability after endotoxemia, but that histamine probably is not the sole mediator of the permeability change.


1983 ◽  
Vol 55 (5) ◽  
pp. 1514-1522 ◽  
Author(s):  
G. C. Kramer ◽  
B. A. Harms ◽  
B. I. Bodai ◽  
E. M. Renkin ◽  
R. H. Demling

We compared the effects of a sustained decrease in plasma oncotic pressure on lung fluid balance with those of an increase in vascular pressure in six unanesthetized sheep. Initial plasma protein concentration of 58.0 +/- 2.2 (SE) mg/ml was quickly reduced to 34.0 +/- 1.4 mg/ml via plasmapheresis and held at this value for 24 h. Red cells were returned with lactated Ringer solution infused at a rate adjusted to maintain central venous pressure; cardiac output and pulmonary vascular pressures also remained at base line. Steady-state lymph flows increased from a base-line value of 8.8 +/- 3.2 to 20.1 +/- 5.6 ml/h, while the lymph-to-plasma protein concentration ratio ( [L/P] ) decreased from 0.65 +/- 0.03 to 0.44 +/- 0.04. Decreased lymph protein resulted in reestablishment of base-line plasma-to-lymph oncotic gradient. The increased lymph flow was not the result of increased filtration forces, since all vascular pressures and the oncotic gradient were unchanged; nor was it due entirely to increased surface area since [L/P] was decreased. The decrease in plasma oncotic pressure, delta pi P, was twice as effective at increasing lymph flow (1.66 ml X h-1 X mmHg-1, delta pi P) as an equivalent increase in microvascular pressure, delta PC, at normal plasma protein concentration (0.82 ml X h-1 X mmHg-1, delta PC). Elevation of microvascular pressure during hypoproteinemia had a greater effect on lymph flow (1.44 ml X h-1 X mmHg-1, delta PC) than at normal plasma protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


1990 ◽  
Vol 259 (1) ◽  
pp. H149-H155 ◽  
Author(s):  
S. K. Lo ◽  
R. R. Garcia-Szabo ◽  
A. B. Malik

We examined the role of leukocytes in the pathogenesis of lung vascular injury induced by thrombin in awake sheep prepared with the lung lymph fistulas. Thrombin (80 U/kg) infusion in control sheep (n = 6) increased pulmonary arterial pressure (Ppa) twofold and pulmonary vascular resistance (PVR) three-fold for the 5-h experimental period. Thrombin also increased pulmonary vascular permeability to protein as assessed by decrease in the reflection coefficient (sigma) from 0.70 +/- 0.03 to 0.61 +/- 0.01. Thrombin caused similar initial pulmonary hemodynamic changes in sheep rendered neutropenic (n = 7; 2% neutrophil count of controls) by treatment with hydroxyurea; however, both Ppa and PVR returned toward base-line values within 120 min postthrombin challenge. The increases in pulmonary lymph flow and transvascular protein clearance also recovered rapidly beginning at 60 min after challenge with thrombin in neutropenic sheep. Neutropenia prevented the increase in lung vascular permeability as the sigma value of 0.71 +/- 0.02 was similar to the control value. Leukocytes isolated from control donor sheep were infused intra-arterially into recipient neutropenic sheep (n = 4) to assess the effects of neutrophil repletion on the pulmonary vascular responses. Thrombin (80 U/kg) challenge infused at 1-3 h after infusion of leukocytes increased lung lymph flow twofold and transvascular protein clearance fourfold and produced increases in Ppa and PVR comparable with the control group. The increases in these parameters were sustained for the 5-h experiment duration. The data indicate the essential pathogenetic role of neutrophils in mediating the thrombin-induced increase in lung vascular permeability.


1986 ◽  
Vol 61 (3) ◽  
pp. 1139-1148 ◽  
Author(s):  
T. A. Hazinski ◽  
R. D. Bland ◽  
T. N. Hansen ◽  
E. G. Sedin ◽  
R. B. Goldberg

To study the influence of plasma protein concentration on fluid balance in the newborn lung, we measured pulmonary arterial and left atrial pressures, lung lymph flow, and concentrations of protein in lymph and plasma of eight lambs, 2–3 wk old, before and after we reduced their plasma protein concentration from 5.8 +/- 0.3 to 3.6 +/- 0.6 g/dl. Each lamb underwent two studies, interrupted by a 3-day period in which we drained protein-rich systemic lymph through a thoracic duct fistula and replaced fluid losses with feedings of a protein-free solution of electrolytes and glucose. Each study consisted of a 2-h control period followed by 4 h of increased lung microvascular pressure produced by inflation of a balloon in the left atrium. Body weight and vascular pressures did not differ significantly during the two studies, but lung lymph flow increased from 2.6 +/- 0.1 ml/h during normoproteinemia to 4.1 +/- 0.1 ml/h during hypoproteinemia. During development of hypoproteinemia, the average difference in protein osmotic pressure between plasma and lymph decreased by 1.6 +/- 2 Torr at normal left atrial pressure and by 4.9 +/- 2.2 Torr at elevated left atrial pressure. When applied to the Starling equation governing microvascular fluid balance, these changes in liquid driving pressure were sufficient to account for the observed increases in lung fluid filtration; reduction of plasma protein concentration did not cause a statistically significant change in calculated filtration coefficient. Protein loss did not influence net protein clearance from the lungs nor did it accentuate the increase in lymph flow associated with left atrial pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)


1980 ◽  
Vol 49 (4) ◽  
pp. 693-699 ◽  
Author(s):  
G. D. Niehaus ◽  
P. T. Schumacker ◽  
T. M. Saba

Lung microvascular permeability in sheep increases during Pseudomonas bacteremia. The sheep's low plasma opsonic fibronectin concentration and associated inefficient reticuloendothelial clearance of blood-borne particulates may contribute to the response of increased lung vascular permeability during sepsis. The present study investigated the influence of sepsis on lung fluid balance in sheep with and without opsonic glycoprotein (plasma fibronectin) deficiency. Using the lung lymph fistula preparation in sheep, we made measurements of lung lymph flow (QLYM), lymph-to-plasma protein concentration ratios (L/P), pulmonary hemodynamics, and extravascular lung water content. Deficiency of opsonic fibronectin resulted in a minimal increase in lymph flow with no change in transvascular protein clearance (QLYM X L/P). Pseudomonas sepsis with or without fibronectin deficiency resulted in a stable L/P and a transient increase in pulmonary arterial pressure, which declined to a new steady state. Although sepsis resulted in a 100% elevation (P < 0.05) in lymph flow and transvascular protein clearance, sepsis in the presence of fibronectin deficiency induced a sustained 300--400% increase in lymph flow and a 300% increase in transvascular protein clearance. Thus opsonic fibronectin deficiency exaggerates the increased lung vascular permeability during sepsis.


1980 ◽  
Vol 239 (1) ◽  
pp. H96-H100
Author(s):  
R. E. Drake ◽  
J. C. Gabel

We estimated the pulmonary capillary membrane filtration coefficient (Kf) and the maximum capillary pressure (PCcritical) at which the lung could maintain a constant weight in 1) 5 control experiments in anesthetized open-chested dogs, 2) 7 experiments in which the dogs were given 3.6-8.3 microgram . kg-1 . min-1 of histamine phosphate, and 3) in 6 experiments after 75-100 mg/kg of alloxan. In additional experiments, pulmonary lymph flow (QL) and protein concentration (CL) were measured during the infusion of histamine and alloxan. After histamine, Kf averaged 0.045 +/- 0,008 ml . min-1mmHg-1 (SE) and PCcritical was 22.1 +/- 1.1 mmHg. These values were not significantly different from the control Kf and PCcritical (0.036 +/- 0.006 and 22.5 +/- 2.3, respectively). After alloxan, Kf (1.43 +/- 0.69) was larger and PCcritical (12.4 +/- 1.3) was significantly less than control (P less than 0.05). Histamine caused no significant change in QL or CL; however, both were increased after alloxan. These results show that Kf, PCcritical, QL, and CL are all changed by an increase in capillary membrane permeability caused by alloxan. Because none of these factors as significantly affected by histamine, dog lung capillary membrane permeability may not be affected by histamine.


1984 ◽  
Vol 247 (1) ◽  
pp. H74-H79 ◽  
Author(s):  
K. Aukland ◽  
G. C. Kramer ◽  
E. M. Renkin

Lymph was collected from tail lymphatics of anesthetized rats, subcutaneous interstitial fluid was obtained by implanting nylon wicks, and tendon interstitial fluid was obtained by centrifugation of pieces of tendon. Spontaneous lymph flow rates averaged 70 nl X min-1 X g skin-1. Protein concentrations and colloid osmotic pressures of sampled fluids differed significantly. Tail lymph had the highest protein concentration relative to plasma [lymph-to-plasma ratio 0.71 +/- 0.03 (SE) n = 10], followed by wick fluid (0.62 +/- 0.02, n = 9), with tendon fluid lowest (0.50 +/- 0.03, n = 10). Albumin and immunoglobulin G (IgG) concentrations in samples of tail skin and tendon were assayed by rocket immunoelectrophoresis. Comparison of their distribution volumes at lymph or tendon fluid concentrations, respectively, with interstitial fluid volumes measured as 2-h 51Cr-ethylenediaminetetraacetic acid space minus 5-min 125I-albumin space indicated that 50-60% of the interstitial volume in these tissues is not available for distribution of albumin or IgG. Low lymph flow and high interstitial protein content of rat tail indicate a slow turnover of interstitial protein. This suggests that interstitial washout of protein plays a role in limiting edema only after a sustained or chronic increase in fluid filtration.


1990 ◽  
Vol 259 (4) ◽  
pp. H1097-H1100 ◽  
Author(s):  
R. K. Reed ◽  
T. C. Laurent ◽  
A. E. Taylor

Hyaluronan, an important structural component of the interstitial matrix in skin, is found in lymph to be subsequently degraded in lymph nodes and liver. Hyaluronan concentration and flux were measured in prenodal lymph from the hindpaw in six pentobarbital-anesthetized mongrel dogs at normal and increased transvascular fluid flux. Lymph flow and hyaluronan concentration in control averaged 16.3 +/- 15.0 (SD) microliters/min (range 6.3-46.5) and 6.16 +/- 3.78 micrograms/ml, respectively. Lymph flow was increased stepwise by raising venous pressure, and measurements were performed at each step after three consecutive and identical measurements of lymph flow and protein concentration taken 15 min apart. Hyaluronan concentration was unchanged until venous pressure was raised above 20 mmHg and then gradually fell to an average of 4.8 +/- 2.67 micrograms/ml at venous pressures around 40 mmHg. The lymphatic hyaluronan flux averaged 0.085 +/- 0.034 micrograms/min in control and 0.28 +/- 0.14 micrograms/min at the highest flows (4.3 times control), draining 2% and 10% of the total interstitial hyaluronan in the tissue in 24 h, respectively. The results suggest that at least part of the hyaluronan in skin is loosely bound and easily removed via lymph.


1980 ◽  
Vol 48 (3) ◽  
pp. 414-420 ◽  
Author(s):  
A. S. Binder ◽  
W. Kageler ◽  
A. Perel ◽  
M. R. Flick ◽  
N. C. Staub

To test whether platelets are necessary for the increased vascular permeability associated with microemboli, we used 16 anesthetized sheep in which we measured lung lymph flow, pulmonary arterial and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentration. Injecting glass bead microemboli (200 micrometers diam) until pulmonary vascular resistance increased to three times base-line values caused lung lymph flow to increase at nearly constant lymph-to-plasma protein concentration ratio that is characteristic of increased microvascular permeability. Antiplatelet serum alone caused transient increases in pulmonary vascular resitance and lung lymph flow, but produced no change in steady-state lung fluid balance. After depleting platelets by greater than 97%, tripling pulmonary vascular resistance with emboli resulted in increases in lung lymph and protein flow comparable to that seen in untreated sheep. We injected twice the amount of beads in thrombocytopenic sheep compared to untreated sheep. We conclude that, although platelets do augment the pulmonary hypertension after emboli, they are not essential for the microemboli vascular injury.


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