Effect of platelet depletion on lung vascular permeability after microemboli in sheep

1980 ◽  
Vol 48 (3) ◽  
pp. 414-420 ◽  
Author(s):  
A. S. Binder ◽  
W. Kageler ◽  
A. Perel ◽  
M. R. Flick ◽  
N. C. Staub
Keyword(s):  
Vascular Permeability ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Plasma Protein ◽  
Protein Concentration ◽  
Lymph Flow ◽  
Plasma Protein Concentration ◽  
Thermodilution Cardiac Output ◽  
Lung Lymph ◽  
Lung Lymph Flow

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.

Isoproterenol and aminophylline reduce lung capillary filtration during high permeability

1979 ◽  
Vol 46 (1) ◽  
pp. 146-151 ◽  
Author(s):  
T. Foy ◽  
J. Marion ◽  
K. L. Brigham ◽  
T. R. Harris
Keyword(s):  
Plasma Protein ◽  
Protein Concentration ◽  
Lymph Flow ◽  
High Permeability ◽  
Plasma Protein Concentration ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Lung Lymph ◽  
Lung Vascular Permeability ◽  
Lung Lymph Flow

Pseudomonas bacteremia in sheep causes a prolonged increase in lung vascular permeability to protein. Isoproterenol and aminophylline could effect lung fluid balance after Pseudomonas by reducing vascular pressures or by blocking release of permeability mediators. We measured vascular pressures, lung lymph flow, and lymph and plasma protein concentrations in unanesthetized sheep under baseline conditions and during steady-state increased permeability after Pseudomonas. Pseudomonas caused pulmonary vascular pressures to rise and lung lymph flow to increase fivefold, but lymph/plasma protein concentration did not change. Pulmonary vascular pressures and lung lymph flow decreased during intravenous infusion of isoproterenol and aminophylline. The decrease in lymph flow after isoproterenol and isoproterenol plus aminophylline was linearly related to the decrease in microvascular pressure (r = 0.71). Lymph/plasma total protein concentration ratios and lymph clearance of proteins with molecular radii 36--96 A remained high during isoproterenol and aminophylline. These drugs can substantially reduce transvascular filtration primarily because they reduce lung vascular pressures.

Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier

1996 ◽  
Vol 81 (4) ◽  
pp. 1730-1738 ◽  
Author(s):  
E. Heidi Jerome ◽  
Keiji Enzan ◽  
Dominique Douguet ◽  
Dachuan Lei ◽  
Gary Jesmok ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Extravascular Lung Water ◽  
Protein Concentration ◽  
Interleukin 2 ◽  
Lymph Flow ◽  
Lung Water ◽  
Plasma Protein Concentration ◽  
Pulmonary Hemodynamics ◽  
Lung Lymph ◽  
Lung Lymph Flow

Jerome, E. Heidi, Keiji Enzan, Dominique Douguet, Dachuan Lei, Gary Jesmok, Carol W. Johnson, Maritza Neuburger, and Norman C. Staub. Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier. J. Appl. Physiol. 81(4): 1730–1738, 1996.—Interleukin-2 (IL-2) is reputed to cause a “vascular leak syndrome.” We studied pulmonary hemodynamics and lymph dynamics in six sheep treated for 7 days with IL-2 (1.8 million IU/kg twice daily or 1.8 million IU/kg each day as a continuous infusion). Lung lymph flow increased from 4.8 ± 2 ml/15 min pre-IL-2 to 14.4 ± 6.8 ml/15 min on the seventh day of IL-2. The lymph-to-plasma protein concentration ratio was unchanged (0.70 ± 0.06 vs. 0.63 ± 0.13). The plasma-to-lymph equilibration half-time of radiolabeled albumin was 2.0 ± 0.6 h pre-IL-2 and 1.0 ± 0.7 h on day 7 of IL-2. Pulmonary arterial pressure was 24 ± 7 cmH2O pre-IL-2, increased to 32 ± 4 cmH2O on the fourth day of IL-2, and returned to 29 ± 5 cmH2O on the seventh day of IL-2. Extravascular lung water was normal (4.07 ± 0.25 g/g dry lung). To clearly determine whether the increase in lung lymph flow was due to hemodynamic changes or to increased leakiness of the microvascular barrier, we volume loaded six sheep with lactated Ringer solution before and after 3 days of IL-2 treatment (1.8 million IU/kg twice daily). Lung lymph flows increased fivefold during 4 h of crystalloid infusion compared with baseline and were higher after 3 days of IL-2. However, lymph-to-plasma protein concentration ratios decreased to the same low levels pre- and post-IL-2 (0.39 ± 0.06 vs. 0.41 ± 0.10), indicating an intact microvascular barrier. Extravascular lung water was elevated (5.56 ± 0.39 g/g dry lung) but was not different from lung water in three volume-loaded control sheep (4.87 ± 0.53 g/g dry lung). We conclude that IL-2 causes minimal or no injury to the pulmonary microvascular barrier and that volume expansion during IL-2 treatment can cause hydrostatic pulmonary edema.

Effect of heparin or fibrinogen depletion on lung fluid balance in sheep after emboli

1979 ◽  
Vol 47 (1) ◽  
pp. 213-219 ◽  
Author(s):  
A. S. Binder ◽  
K. Nakahara ◽  
K. Ohkuda ◽  
W. Kageler ◽  
N. C. Staub
Keyword(s):  
Vascular Permeability ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Fluid Balance ◽  
Lymph Flow ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Lung Lymph ◽  
Lung Vascular Permeability ◽  
Lung Lymph Flow

Investigators have proposed that fibrinogen, fibrin, or their degradation products are essential for the increased lung vascular permeability to fluid and protein that may occur after microemboli. To test this hypothesis, we used 20 anesthetized ventilated sheep in which we measured lung lymph flow, pulmonary artery and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentrations. We injected glass bead microemboli (200 micrometers diam) sufficient to raise pulmonary vascular resistance to three times base-line values and cause increased lung lymph flow with a parallel increase in protein clearance, which is characteristic of increased lung vascular permeability. Neither large doses of heparin (3,000 U/kg) nor fibrinogen depletion with viper venom (ancrod, 2 U/kg), by themselves, affected steady-state pulmonary hemodynamics or lung fluid balance. These treatments prior to giving sufficient amounts of emboli to triple the pulmonary vascular resistance did not prevent the increased lung vascular permeability. We conclude that neither fibrin deposition nor degradation are essential to microembolic lung vascular injury in sheep.

Effect of hypoproteinemia on lung fluid balance in awake newborn lambs

1986 ◽  
Vol 61 (3) ◽  
pp. 1139-1148 ◽  
Author(s):  
T. A. Hazinski ◽  
R. D. Bland ◽  
T. N. Hansen ◽  
E. G. Sedin ◽  
R. B. Goldberg
Keyword(s):  
Plasma Protein ◽  
Fluid Balance ◽  
Left Atrial ◽  
Protein Concentration ◽  
Lymph Flow ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Plasma Protein Concentration ◽  
Lung Fluid ◽  
Lung Lymph

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)

Hindlimb and lung lymph flows during prolonged exercise

1993 ◽  
Vol 75 (2) ◽  
pp. 633-638 ◽  
Author(s):  
G. Coates ◽  
H. O'Brodovich ◽  
G. Goeree
Keyword(s):  
Steady State ◽  
Surface Area ◽  
Vascular Resistance ◽  
Plasma Protein ◽  
Concentration Ratio ◽  
Protein Concentration ◽  
Plasma Protein Concentration ◽  
Efferent Duct ◽  
Exercise Period ◽  
Lung Lymph

We performed experiments to determine the effect of 2h of exercise on hindlimb lymph flow (QL) and protein concentration in sheep. We compared these results with the lung QL response to long-term exercise. Eleven sheep with catheters in an efferent duct of a prefemoral lymph node and 12 sheep with chronic lung lymph catheters exercised at 2.5–3.0 km/h for up to 2h (lung lymph: range 45–120 min, mean 80 min;hindlimb lymph: range 75–120 min, mean 110.5 min). Cardiac output approximately doubled. Pulmonary vascular resistance decreased by 42%, and systemic vascular resistance decreased by 35%. There were small increases in calculated pulmonary microvascular and arterial pressures. During steady-state exercise, lung QL doubled and the lung lymph-to-plasma protein concentration ratio decreased by 16%. There was an immediate fivefold increase in hindlimb QL, and the hindlimb lymph-to-plasma protein concentration ratio decreased by 26%. Hindlimb QL decreased to a constant 130% above baseline during the last 30 min of exercise. We conclude that the marked increase in hindlimb QL early in exercise is secondary to a massaging effect in working muscles. The steady-state increases in QL toward the end of the exercise period in both lung and hindlimb are secondary to both increased surface area and pressure in the pulmonary and systemic microvascular circulations. Our data suggest that in the lung the major factor determining QL is increased vascular surface area.

Effect of isoproterenol or exercise on pulmonary lymph flow and hemodynamics

1986 ◽  
Vol 60 (1) ◽  
pp. 38-44 ◽  
Author(s):  
H. O'Brodovich ◽  
G. Coates
Keyword(s):  
Cardiac Output ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Lymph Flow ◽  
Pulmonary Hemodynamic ◽  
Vascular Catheters ◽  
Exercise Induced ◽  
Response To Exercise ◽  
Lung Lymph ◽  
Lung Lymph Flow

Experiments were performed to determine whether different methods of increasing cardiac output would have similar effects on lung lymph flow, and to assess the contribution of the microvasculature (fluid-exchanging vessels) to the total calculated pulmonary vascular resistance. Yearling unanesthetized sheep with chronic vascular catheters and lung lymph fistulas underwent intravenous infusions of isoproterenol at 0.2 micrograms X kg-1. min-1 (n = 8) or were exercised on a treadmill (n = 16). Both isoproterenol and exercise increased cardiac output, lowered calculated total pulmonary and systemic vascular resistances, and had no effect on the calculated pulmonary microvascular pressure. Isoproterenol infusions did not affect lung lymph flow, whereas exercise increased lung lymph flow in proportion to the increase in cardiac output. We conclude that 1) the sheep has a different pulmonary hemodynamic response to exercise than dogs and man, 2) the microvasculature is recruited during exercise-induced but not isoproterenol-induced increases in cardiac output, and 3) the microvasculature represents only a small proportion of the total calculated pulmonary vascular resistance.

Lung lymph and free interstitial fluid protein composition in sheep with edema

1976 ◽  
Vol 230 (6) ◽  
pp. 1650-1653 ◽  
Author(s):  
CR Vreim ◽  
PD Snashall ◽  
RH Demling ◽  
NC Staub
Keyword(s):  
Plasma Protein ◽  
Protein Concentration ◽  
Interstitial Fluid ◽  
Protein Composition ◽  
Lymph Flow ◽  
Base Line ◽  
Interstitial Edema ◽  
Plasma Protein Concentration ◽  
Free Interstitial ◽  
Lung Lymph

In 10 anesthetized sheep with mild or moderate pulmonary edema we determined whether the protein composition of lung lymph is representative of free interstitial fluid. We measured protein concentration and albumin fraction in 1-mul samples of plasma, lung lymph, and free interstitial fluid. We also measured lung lymph flow. In five sheep with edema caused by increased pulmonary microvascular pressure, the average (+/- 1 SE) plasma protein concentration was 6.0 +/- 0.4 g/100 ml, lung lymph 3.4 +/- 0.2, and interstitial fluid 3.1 +/- 0.3. Lymph flow increased from an average base-line value of 9.4 ml/h to 43.4 ml/h during edema. Average albumin fractions in lymph and interstitial fluid were 0.56 +/- 0.02 and 0.50 +/- 0.01, respectively, compared with 0.44 +/- 0.01 for plasma. In five sheep with increased-permeability edema, average plasma protein concentration was 5.7 +/- 0.3 g/100 ml, lung lymph 4.1 +/- 0.4, and interstitial fluid 4.6 +/- 0.4. Base-line lymph flow was 11.0 ml/h and increased to 27.8 ml/h during edema. Average albumin fractions in lymph and interstitial fluid were 0.53 +/- 0.01 and 0.50 +/- 0.02, respectively, compared with 0.43 +/- 0.01 for plasma. We conclude in both high-pressure and altered-permeability edema, the protein composition of lung lymph collected from the major lung efferent lymphatic is representative of the free interstitial edema fluid.

Intravascular macrophage depletion attenuates endotoxin lung injury in anesthetized sheep

1999 ◽  
Vol 87 (4) ◽  
pp. 1354-1359 ◽  
Author(s):  
Yasuyuki Sone ◽  
Vladimir B. Serikov ◽  
Norman C. Staub
Keyword(s):  
Protein Concentration ◽  
Pulmonary Arterial Pressure ◽  
Lymph Flow ◽  
Plasma Protein Concentration ◽  
Macrophage Population ◽  
Protein Clearance ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Pulmonary Intravascular Macrophages ◽  
Lung Lymph Flow

We recently showed that we can selectively and safely deplete most (average 85%) of the pulmonary intravascular macrophages in sheep by intravenously infusing liposomes containing dichloromethylene bisphosphonate. After a 1-h stable baseline, we made a 6-h comparison after a 30-min intravenous endotoxin infusion (1 μg/kg) between six anesthetized control lambs and six anesthetized lambs in which the intravascular macrophages had been depleted 24 h previously. Three of the control lambs had been macrophage depleted and allowed to recover their intravascular macrophage population for ≥2 wk. After depletion, both the early and late pulmonary arterial pressure rises were dramatically attenuated. Our main interest, however, was in the acute lung microvascular injury response. The early and late rises in lung lymph flow and the increase in lung lymph protein clearance (lymph flow × lymph-to-plasma protein concentration ratio) were >90% attenuated. We conclude the pulmonary intravascular macrophages are responsible for most of the endotoxin-induced pulmonary hypertension and increased lung microvascular leakiness in sheep, although the unavoidable injury of other intravascular macrophages by the depletion regime may also contribute something.

Arachidonate raises vascular resistance but not permeability in lungs of awake sheep

1980 ◽  
Vol 48 (4) ◽  
pp. 581-586 ◽  
Author(s):  
M. L. Ogletree ◽  
K. L. Brigham
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Permeability ◽  
Protein Concentration ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Plasma Protein Concentration ◽  
Pulmonary Vasoconstriction ◽  
Lung Lymph ◽  
Lung Vascular Permeability ◽  
Lung Lymph Flow

Prostaglandins have been implicated as mediators of pulmonary hypertension in a variety of reactions, but the agents responsible for pathological increases in lung vascular permeability have not been determined. To test the hypothesis that products of arachidonic acid metabolism produce pulmonary vasoconstriction and alter lung vascular permeability, we infused purified sodium arachidonate (25-100 micrograms . kg-1 . min-1) into chronically instrumented unanesthetized sheep prepared for collection of lung lymph. Arachidonate produced dose-related increases in pulmonary artery pressure and lung lymph flow with corresponding decreases in the lymph-to-plasma protein concentration ratio. Lung lymph responses were like those caused by mechanically elevating left atrial pressure. Infusion of indomethacin or sodium eicosatetraynoate inhibited hemodynamic and lung lymph responses to arachidonate. We conclude a) that arachidonate must be converted to prostaglandin cyclic endoperoxides to produce pulmonary hypertension and increased flow of protein-poor lung lymph and b) that under normal conditions, no detectable increase in lung vascular permeability results from either arachidonate itself or the combined products of arachidonate metabolism via cyclooxygenase and/or lipoxygenase.

Effect of complement activation with cobra venom factor on pulmonary vascular permeability

1986 ◽  
Vol 61 (6) ◽  
pp. 2202-2209 ◽  
Author(s):  
A. Johnson ◽  
J. A. Cooper ◽  
A. B. Malik
Keyword(s):  
Vascular Permeability ◽  
Plasma Protein ◽  
Complement Activation ◽  
Concentration Ratio ◽  
Protein Concentration ◽  
Cobra Venom ◽  
Plasma Protein Concentration ◽  
Cobra Venom Factor ◽  
Pulmonary Vascular Permeability ◽  
Protein Clearance

We examined the effect of acute complement activation on lung vascular permeability to proteins in awake sheep prepared with lung lymph fistulas. Complement was activated by cobra venom factor (CVF) infusion (400 U/kg for 1 h iv). Studies were made in two groups of sheep: 1) infusion of CVF containing the endogenous phospholipase A2 (PLA2) (n = 6); and 2) infusion of CVF pretreated with bromophenacyl bromide to inhibit PLA2 activity (n = 5). Intravascular complement activation transiently increased mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) in both groups. Pulmonary lymph flow (Qlym) and lymph protein clearance (Qlym X lymph-to-plasma protein concentration ratio) were also transiently increased in both groups. Pulmonary vascular permeability to proteins was assessed by raising left atrial pressure and determining the lymph-to-plasma protein concentration ratio (L/P) at maximal Qlym. In both groups the L/P at maximal Qlym was not different from normal. In a separate group (n = 4), CVF-induced complement activation was associated with 111In-oxine granulocyte sequestration in the lungs. In vitro plasma from CVF-treated animals aggregated neutrophils but did not stimulate neutrophils to produce superoxide anion generation. Therefore, CVF-induced complement activation results in pulmonary neutrophil sequestration and in increases in PVR and lymph protein clearance. The increase in lymph protein clearance is due to increased pulmonary microvascular pressure and not increased vascular permeability to proteins.

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