CVF-induced decomplementation: effect on lung transvascular protein flux after thrombin

1987 ◽  
Vol 62 (3) ◽  
pp. 863-869 ◽  
Author(s):  
A. Johnson ◽  
S. K. Lo ◽  
F. B. Blumenstock ◽  
A. B. Malik
Keyword(s):  
Plasma Protein Concentration ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Protein Clearance ◽  
Pulmonary Arterial ◽  
Hemolytic Complement Activity ◽  
The Mean ◽  
Lung Lymph ◽  
Made In ◽  
Protein Exchange

We examined the effects of cobra venom factor (CVF) on the changes in pulmonary hemodynamics and transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in unanesthetized sheep prepared with lung lymph fistulas. The animals received tranexamic acid (100 mg) to suppress fibrinolysis and were then challenged with an intravenous infusion of alpha-thrombin (80 U/kg). Control-thrombin challenged sheep were compared with the CVF-treated sheep challenged with the same thrombin dosage. CVF treatment (187 U X kg-1 X day-1 for 4 days) decreased the total hemolytic complement activity by 45% of control. Thrombin infusion in control sheep increased the mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and lymph protein clearance (pulmonary lymph flow X lymph-to-plasma protein concentration ratio, Clym). Thrombin infusion in CVF-treated sheep produced smaller increments in Ppa, PVR, and Clym. Pulmonary lymph obtained from control-thrombin and CVF-thrombin sheep induced migration of granulocytes obtained from normal unchallenged sheep. The granulocytes obtained from CVF-treated sheep responded relatively less to the migratory and O-2-generating stimuli (i.e., zymosan-treated serum, pulmonary lymph from sheep after thrombin challenge, and plasma from sheep after CVF treatment) compared with normal granulocytes. The attenuation of the thrombin-induced increases in Ppa, PVR, and lung transvascular fluid and protein exchange by CVF treatment may be the result of impaired function of granulocytes.

Effect of pulmonary arterial occlusion on lung fluid and protein exchange

1982 ◽  
Vol 53 (3) ◽  
pp. 543-548 ◽  
Author(s):  
P. S. Barie ◽  
A. B. Malik
Keyword(s):  
Protein Concentration ◽  
Arterial Occlusion ◽  
Base Line ◽  
Plasma Protein Concentration ◽  
Lung Fluid ◽  
Mean Pulmonary Arterial Pressure ◽  
Protein Clearance ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Protein Exchange

We examined the effects of left pulmonary arterial occlusion and reperfusion on pulmonary transvascular fluid and protein exchange in the sheep lung lymph fistula preparation. Pulmonary lymph flow (Qlym) increased from the base-line value of 5.0 +/- 0.8 to 10.0 +/- 2.1 ml/h after occlusion (P less than 0.05); the steady-state value of 11.9 +/- 2.2 ml/h during reperfusion was not significantly different from the value during occlusion. The lymph-to-plasma protein concentration ratio (L/P) did not change significantly during either occlusion or reperfusion. Transvascular protein clearance (Qlym X L/P) increased from 3.7 +/- 0.6 to 8.4 +/- 2.1 ml/h during occlusion (P less than 0.05) and remained elevated at 8.6 +/- 1.7 ml/h during reperfusion. The sustained increases in Qlym and protein clearance could not be explained by the 3-Torr increase in mean pulmonary arterial pressure during the occlusion period or by an increase in the interstitial protein concentration caused by a period of decreased filtration during occlusion. The increases in protein clearance that occurred with increased Qlym during occlusion and reperfusion were greater than the increases in protein clearance with comparably increased Qlym during left atrial hypertension. The results suggest that occlusion of a pulmonary artery increases vascular permeability to plasma proteins in the lung.

Influence of opsonic fibronectin deficiency on lung fluid balance during bacterial sepsis

1980 ◽  
Vol 49 (4) ◽  
pp. 693-699 ◽  
Author(s):  
G. D. Niehaus ◽  
P. T. Schumacker ◽  
T. M. Saba
Keyword(s):  
Vascular Permeability ◽  
Fluid Balance ◽  
Lymph Flow ◽  
Plasma Protein Concentration ◽  
Pulmonary Hemodynamics ◽  
Lung Fluid ◽  
Protein Clearance ◽  
Lung Fluid Balance ◽  
Lung Lymph ◽  
Lung Vascular Permeability

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.

Does ADP-Induced Platelet Aggregation Mediate Lung Vascular Injury?

1981 ◽  
Author(s):  
A B Malik ◽  
F L Minnear ◽  
M V Tahamont ◽  
D G Moon ◽  
J E Kaplan
Keyword(s):  
Platelet Aggregation ◽  
Vascular Injury ◽  
Protein Concentration ◽  
Control Group ◽  
Plasma Protein Concentration ◽  
Fluid Filtration ◽  
Lung Fluid ◽  
Protein Clearance ◽  
Pulmonary Arterial ◽  
Protein Exchange

We determined the effects of ADP-induced platelet aggregation on lung fluid and protein exchange to examine whether platelet aggregation mediates lung vascular injury. The studies were made in intact sheep in which pulmonary lymph was obtained, and the protein concentration of lymph was compared to that of plasma. Two groups were studied: Control sheep receiving i.v. infusion of 10 mg/kg of ADP and experimental sheep in which platelets were depleted with anti-platelet serum prior to ADP infusion. In the control group, ADP decreased the platelet count from 178,554 ± 62,750 to 103,500 ± 47,828 cells/mm3, suggesting the entrapment of platelet in the pulmonary circulation. The pulmonary arterial pressure (Ppa) increased from 13.1 ± 1.8 to 15.9 ± 1.2 mmHg. Lung lymph flow (Qlym) increased from 8.4 ± 1.8 to 11.4 ± 2.3ml/hr (p < 0.05) and transvascular protein clearance (Qlym x lymph/plasma protein concentration), a measure of protein exchange, increased from 6.7 ± 1.3 to 9.4 ± 3.0 ml/hr (p < 0.05). These increases could be explained by an increase in microvascular pressure (Pmv) and ultrafiltration since mechanically elevation of Pmv produced the same changes in Qlym and clearance. Platelet depletion prevented the ADP-induced increases in platelet aggregation does not mediate lung vascular injury, but increases fluid filtration by increasing the microvascular pressure. This effect may be mediated by release of pulmonary vasoconstrictor substances such as thromboxane A2 and serotonin after platelet aggregation.

Effect of prostacyclin on pulmonary vascular response to thrombin in awake sheep

1986 ◽  
Vol 60 (2) ◽  
pp. 546-553 ◽  
Author(s):  
M. B. Perlman ◽  
S. K. Lo ◽  
A. B. Malik
Keyword(s):  
Platelet Aggregation ◽  
Control Group ◽  
In Vitro Tests ◽  
Neutrophil Chemotaxis ◽  
Plasma Protein Concentration ◽  
Platelet Counts ◽  
Protein Clearance ◽  
Pulmonary Arterial ◽  
Made In

We determined the effects of infusion of prostacyclin (PGI2) and 6-alpha-carba-PGI2 (6-cPGI2), a stable PGI2 analogue, on pulmonary transvascular fluid and protein fluxes after intravascular coagulation induced by thrombin. Studies were made in control awake sheep prepared with lung lymph fistulas (n = 6) and in similarly prepared awake sheep pretreated with either 6-cPGI2 (n = 5) or PGI2 (n = 5). Both prostacyclin compounds (500 ng X kg-1 X min-1) were infused intravenously. All groups were challenged with 80 U/kg thrombin. Pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), pulmonary lymph flow (Qlym), lymph protein clearance (Qlym X lymph/plasma protein concentration ratio), and neutrophil and platelet counts were determined. In vitro tests assessed sheep neutrophil chemotaxis and chemiluminescence and platelet aggregation. In both 6-cPGI2 and PGI2 groups, the increases in Qlym after thrombin were less than those in the control group. The increase in lymph protein clearance in the 6-cPGI2 group was the same as that in control, whereas the increase in clearance in the PGI2 group was reduced. PVR and Ppa increased to a greater extent in the 6-cPGI2 group than in the control group, whereas the increases in PVR and Ppa were inhibited in the PGI2 group. Neutrophil and platelet counts decreased after thrombin in PGI2 and 6-cPGI2 groups, as they did in the control group. Neither 6-cPGI2 altered neutrophil chemotaxis induced by thrombin and chemiluminescence induced by opsonized zymosan. Both prostacyclin compounds inhibited platelet aggregation induced by ADP or thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective lung leukosequestration after complement activation

1988 ◽  
Vol 65 (1) ◽  
pp. 80-88 ◽  
Author(s):  
J. M. Klausner ◽  
L. Kobzik ◽  
C. R. Valeri ◽  
D. Shepro ◽  
H. B. Hechtman
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Pulmonary Arterial Pressure ◽  
Superior Vena ◽  
Vena Cava ◽  
Protein Ratio ◽  
Mean Pulmonary Arterial Pressure ◽  
Protein Clearance ◽  
Leukocyte Counts ◽  
Pulmonary Arterial ◽  
Lung Lymph

This study tests whether activated complement leads to a selective entrapment of polymorphonuclear leukocytes (PMN's) in the lungs. Awake sheep were infused for 5 min with zymosan-activated plasma (ZAP, 2.5 mg/ml) at a rate of 5 ml/min into the superior vena cava (IV, n = 4) or intra-arterially into the aortic arch or femoral artery (IA, n = 8). At the end of IV infusion, leukocyte counts fell from 8,862 to 1,631/mm3 (P less than 0.01). PMN counts across the lungs decreased by 74%. There were increases in plasma thromboxane (Tx) B2 from 114 to 2,733 pg/ml (P less than 0.01), mean pulmonary arterial pressure from 12 to 42 mmHg (P less than 0.01), and physiological shunt from 13 to 25% (P less than 0.05). Within 1 h lymph TxB2 levels had risen from 301 to 4,916 pg/ml (P less than 0.01), lung lymph flow (QL) rose from 3.7 to 11.1 ml/30 min (P less than 0.05), lymph-to-plasma protein ratio (L/P) remained unchanged at 0.63, and lymph protein clearance increased from 2.3 to 7.5 ml/30 min (P less than 0.05). Leukosequestration, quantitated by capillary PMN counting and by assaying the granulocyte marker myeloperoxidase, occurred relative to sham animals (P less than 0.05) in the lung and spleen but not in other organs. Intra-arterial ZAP infusion led to changes that were similar in magnitude and timing to the IV group.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

A computed method for noninvasive MRI assessment of pulmonary arterial hypertension

2004 ◽  
Vol 96 (2) ◽  
pp. 463-468 ◽  
Author(s):  
Eric Laffon ◽  
Christophe Vallet ◽  
Virginie Bernard ◽  
Michel Montaudon ◽  
Dominique Ducassou ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Cross Sectional Area ◽  
Physical Parameters ◽  
Sectional Area ◽  
Biophysical Parameters ◽  
Cross Sectional ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
The Mean

The present method enables the noninvasive assessment of mean pulmonary arterial pressure from magnetic resonance phase mapping by computing both physical and biophysical parameters. The physical parameters include the mean blood flow velocity over the cross-sectional area of the main pulmonary artery (MPA) at the systolic peak and the maximal systolic MPA cross-sectional area value, whereas the biophysical parameters are related to each patient, such as height, weight, and heart rate. These parameters have been measured in a series of 31 patients undergoing right-side heart catheterization, and the computed mean pulmonary arterial pressure value (PpaComp) has been compared with the mean pressure value obtained from catheterization (PpaCat) in each patient. A significant correlation was found that did not differ from the identity line PpaComp = PpaCat ( r = 0.92). The mean and maximal absolute differences between PpaComp and PpaCat were 5.4 and 11.9 mmHg, respectively. The method was also applied to compute the MPA systolic and diastolic pressures in the same patient series. We conclude that this computed method, which combines physical (whoever the patient) and biophysical parameters (related to each patient), improves the accuracy of MRI to noninvasively estimate pulmonary arterial pressures.

PEEP inhibits hypoxic pulmonary vasoconstriction in dogs

1991 ◽  
Vol 70 (4) ◽  
pp. 1867-1873 ◽  
Author(s):  
P. Lejeune ◽  
J. L. Vachiery ◽  
J. M. De Smet ◽  
M. Leeman ◽  
S. Brimioulle ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Intact Animal ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Balloon Catheter ◽  
Vena Cava ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial

The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of edema and hemodynamic changes on extravascular thermal volume of the lung

1984 ◽  
Vol 56 (4) ◽  
pp. 878-890 ◽  
Author(s):  
B. A. Gray ◽  
R. C. Beckett ◽  
R. C. Allison ◽  
D. R. McCaffree ◽  
R. M. Smith ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Mean Transit Time ◽  
Hemodynamic Changes ◽  
Pulmonary Hemodynamics ◽  
Indocyanine Green Dye ◽  
Pulmonary Arterial ◽  
The Mean ◽  
The Difference ◽  
Acute Changes ◽  
Thermal Dilution

The extravascular thermal volume of the lung (ETV) has been measured in dogs as the difference between mean transit time (t) volumes for heat and indocyanine green dye across the pulmonary circulation, calculated as the product of thermal dilution cardiac output (CO) and the difference in t for aortic indicator-dilution curves generated by right and left atrial injections. ETV measurements were compared with the extravascular lung mass (ELM): in 21 normal dogs, ETV/ELM = 1.11 +/- 0.14 (SD); in 17 dogs with hydrostatic pulmonary edema (up to 21 g/kg), ETV/ELM = 0.90 +/- 0.11; and in 27 dogs with alloxan pulmonary edema (up to 51 g/kg); ETV/ELM = 0.93 +/- 0.13. For all 65 dogs the mean ETVELM was 0.98 +/- 0.15, and the liner regression was ETV (ml/kg) = 0.90 ELM (g/kg) + 0.86 +/- 2.25 (SEE; r = 0.96). Calculations based on measurements of lung specific heat predict that ETV/ELM should equal 0.984. With acute changes in pulmonary hemodynamics, ETV was reduced by reductions in pulmonary arterial pressure (Ppa) sufficient to produce zone 1 conditions at the top of the lung. However, ETV was not affected by increases in CO (mean = 50%) produced by nitroprusside or by increases in Ppa and pulmonary blood volume (mean = 27%) produced by partial mitral valve obstruction. Distortion of the thermal dilution curve due to position of the arterial thermistor appears to be the greatest source of variability and overestimation. Simultaneous measurements from pairs of thermistors differed by 14% (range 0.4–50%).

The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep

1989 ◽  
Vol 67 (3) ◽  
pp. 202-206 ◽  
Author(s):  
Michele Smith ◽  
Geoffrey Coates ◽  
J. Michael Kay ◽  
Hugh O'Brodovich
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hemodynamic Response ◽  
Pulmonary Hemodynamics ◽  
Vascular Reserve ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Increased Blood Flow

Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure–flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 μm diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.Key words: pulmonary hypertension, pneumonectomy, sheep.

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