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 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.

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)

Effects of different-size microemboli on lung fluid and protein exchange

1981 ◽  
Vol 51 (2) ◽  
pp. 461-464 ◽  
Author(s):  
A. Johnson ◽  
A. B. Malik
Keyword(s):  
Hydrostatic Pressure ◽  
Pulmonary Arteries ◽  
Plasma Protein Concentration ◽  
Fluid Filtration ◽  
Lung Fluid ◽  
Collateral Arteries ◽  
Branching Points ◽  
Micron Diameter ◽  
Lung Lymph ◽  
Protein Exchange

We examined the effects of embolization with different-size glass-bead microemboli on pulmonary transvascular fluid and protein exchange in the sheep lung lymph fistula preparation. Embolization with either 200- or 500-micron-diameter glass beads caused comparable increases in pulmonary vascular resistance, which were sustained for the duration of the study. The 200-micron beads increased pulmonary lymph flow (Qlym) and did not affect the lymph-to-plasma protein concentration ratio (L/P), whereas injection with 500-micron beads increased Qlym and decreased L/P. The latter changes were comparable to those observed after an increase in pulmonary microvascular pressure induced by left atrial hypertension, suggesting that the 500-micron beads increase the Qlym by raising the microvascular hydrostatic pressure. In contrast, the 200-micron beads increased the transvascular clearance of proteins to a greater extent, since L/P did not decrease as Qlym increased. These findings suggest that lung vascular permeability increases after embolization with smaller (200-micron) but not with larger (500-micron) emboli. The increased permeability after embolization with small beads may be due to transmission of the permeability-increasing substances to the downstream capillaries via the collateral pulmonary arteries. This would not occur after embolization with larger emboli if these obstructed the pulmonary arteries upstream from branching points of the collateral arteries. The ultrafiltration of protein-poor plasma after embolization with the 500-micron beads may reflect increased fluid filtration in unobstructed microvessels due to increase in the microvascular hydrostatic pressure.

Beta-adrenergic modulation of pulmonary transvascular fluid and protein exchange

1986 ◽  
Vol 60 (1) ◽  
pp. 266-274 ◽  
Author(s):  
F. L. Minnear ◽  
A. Johnson ◽  
A. B. Malik
Keyword(s):  
Control Group ◽  
Protective Effects ◽  
Beta Adrenergic ◽  
Intravascular Coagulation ◽  
Protein Clearance ◽  
Adrenergic Antagonist ◽  
Adrenergic Modulation ◽  
Pulmonary Arterial ◽  
Beta Adrenergic Agonist ◽  
Protein Exchange

We determined in anesthetized sheep whether isoproterenol, a beta-adrenergic agonist, prevents the increases in pulmonary fluid and protein exchange produced by thrombin-induced intravascular coagulation. Seven sheep were infused intravenously with 0.05 micrograms X kg-1 X min-1 isoproterenol before infusion of alpha-thrombin, and six sheep were infused with alpha-thrombin only and served as control subjects. The marked increases in pulmonary lymph flow and lymph protein clearance in the control thrombin group were attenuated (P less than 0.05) in the isoproterenol group in association with a higher pulmonary blood flow (P less than 0.05) and a lower pulmonary vascular resistance (P less than 0.05) in the isoproterenol group and with similar increases in pulmonary arterial and pulmonary arterial wedge pressures in both groups. The decreases in fluid and protein fluxes produced by isoproterenol are related to its beta-adrenergic properties because propranolol, a beta-adrenergic antagonist, blocked the protective effects of isoproterenol in a second group of sheep infused with propranolol, isoproterenol, and thrombin. Raising left atrial pressure to test for changes in vascular permeability increased protein flux to a much greater extent in the thrombin control group than in the isoproterenol group challenged with thrombin. The data suggest that isoproterenol attenuated the increase in fluid and protein fluxes produced by thrombin-induced intravascular coagulation by a permeability-decreasing mechanism.

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.

Thrombin-induced alterations in lung fluid balance in awake sheep

1985 ◽  
Vol 58 (5) ◽  
pp. 1421-1427 ◽  
Author(s):  
S. K. Lo ◽  
M. B. Perlman ◽  
G. D. Niehaus ◽  
A. B. Malik
Keyword(s):  
Tranexamic Acid ◽  
Vascular Permeability ◽  
Intravenous Infusion ◽  
Treated Group ◽  
Control Group ◽  
Base Line ◽  
Plasma Protein Concentration ◽  
Lung Fluid ◽  
Mean Pulmonary Arterial Pressure ◽  
Protein Clearance

We examined the effect of fibrinolysis depression on thrombin-induced pulmonary microembolism in awake sheep prepared with chronic lung lymph fistulas. Fibrinolysis was depressed by an intravenous infusion (100 mg) of tranexamic acid [trans-4-(Aminomethyl)cyclohexanecarboxylic acid]. Pulmonary microembolism was induced by an intravenous infusion of alpha-thrombin (80 NIH U/kg) in normal (n = 7) and in tranexamic acid-treated (n = 6) sheep. Thrombin immediately increased pulmonary lymph flow (Qlym) in both groups. The increased Qlym was not associated with a change in the lymph-to-plasma protein concentration (L/P) ratio in the control group and with a small decrease in the tranexamic acid-treated group. The increases in Qlym and pulmonary transvascular protein clearance (Qlym X L/P ratio) in the tranexamic acid-treated group were greater and sustained at four- to fivefold above base line for 10 h after the thrombin and remained elevated at twofold above base line even at 24 h. In contrast, Qlym and protein clearance were transiently increased in the control group. The mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) increased after thrombin in tranexamic acid-treated group; the increases in Ppa and PVR in the control group were transient. Protein reflection coefficient as determined by the filtration independent method decreased after thrombin in tranexamic acid-treated sheep (n = 5), indicating an increased vascular permeability to proteins. We conclude that prolongation of microthrombi retention in the pulmonary circulation results in an increased vascular permeability to proteins. Both increased vascular permeability and vascular hydrostatic pressure are important determinants of the increases in Qlym and transvascular protein clearance after thrombin-induced pulmonary microembolism.

Lung fluid balance, vascular permeability, and gas exchange after acid aspiration in awake goats

1984 ◽  
Vol 56 (4) ◽  
pp. 979-985 ◽  
Author(s):  
R. Winn ◽  
J. Stothert ◽  
B. Nadir ◽  
J. Hildebrandt
Keyword(s):  
Protein Concentration ◽  
Base Line ◽  
Lung Water ◽  
Plasma Protein Concentration ◽  
Acid Aspiration ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Lung Injuries ◽  
Pulmonary Arterial ◽  
Lung Lymph

Lung injuries were produced by instilling 2.5 ml/kg of 0.1 N HCl into the trachea of lightly anesthetized goats with previously implanted lung lymph fistulas. Lymph flow (QL), lymph-to-plasma protein concentration ratio (L/P), pulmonary arterial and wedge pressures (Ppa, Pw), percent shunt (Qs/QT), and postmortem extravascular lung water (EVLW) were then measured for up to 48 h. QL began to increase within 15 min of injury from a baseline value of 7.2 ml/h to reach a peak of 231% of base line by 1.5 h, then decreased to 160% at 24 h and returned to base line by 48 h. Average L/P increased from 0.66 to a peak of 0.73 at 2 h. Ppa increased from 17.0 cmH2O to a first peak of 25.3 cmH2O at 15 min, then decreased to base line by 75 min. There was a second rise that peaked at 3 h before returning to base line at 24–48 h; Pw was unchanged throughout. Qs/QT increased from 8.5 to a peak of 34% at 1 h, then decreased to 15% at 4 h, and stabilized at 17–20% at 48 h. EVLW was 237% of base line at 4 h and declined somewhat but remained elevated at 194% of base line at 24 and 48 h. Qs/QT was less than expected based on the reduction in lung volume after aspiration. We conclude that microvascular permeability was increased after acid and that a protective vasoconstriction, probably due to local hypoxia, directed blood away from nonventilated alveoli.

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.

Effects of hypoproteinemia-induced myocardial edema on left ventricular function

1998 ◽  
Vol 274 (3) ◽  
pp. H937-H944 ◽  
Author(s):  
M. Miyamoto ◽  
D. E. McClure ◽  
E. R. Schertel ◽  
P. J. Andrews ◽  
G. A. Jones ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Protein Concentration ◽  
Systolic Dysfunction ◽  
Myocardial Edema ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Stroke Work ◽  
Plasma Protein Concentration ◽  
Total Plasma Protein

In previous studies, we observed left ventricular (LV) systolic and diastolic dysfunction in association with interstitial myocardial edema (IME) induced by either coronary venous hypertension (CVH) or lymphatic obstruction. In the present study, we examined the effects of myocardial edema induced by acute hypoproteinemia (HP) on LV systolic and diastolic function. We also combined the methods of HP and CVH (HP-CVH) to determine their combined effects on LV function and myocardial water content (MWC). We used a cell-saving device to lower plasma protein concentration in HP and HP-CVH groups. CVH was induced by inflating the balloon in the coronary sinus. Six control dogs were treated to sham HP. Conductance and micromanometer catheters were used to assess LV function. Contractility, as measured by preload recruitable stroke work, did not change in control or HP groups but declined significantly (14.5%) in the HP-CVH group. The time constant of isovolumic LV pressure decline (τ) increased significantly from baseline by 3 h in the HP (24.8%) and HP-CVH (27.1%) groups. The end-diastolic pressure-volume relationship (stiffness) also increased significantly from baseline by 3 h in the HP (78.6%) and HP-CVH (42.6%) groups. Total plasma protein concentration decreased from 5.2 ± 0.2 g/dl at baseline to 2.5 ± 0.0 g/dl by 3 h in the HP and HP-CVH groups. MWC of the HP (79.8 ± 0.25%) and HP-CVH groups (79.8 ±0.2%) were significantly greater than that of the control group (77.8 ± 0.3%) but not different from one another. In conclusion, hypoproteinemia-induced myocardial edema was associated with diastolic LV dysfunction but not systolic dysfunction. The edema caused by hypoproteinemia was more than twice that produced by our previous models, yet it was not associated with systolic dysfunction. CVH had a negative inotropic effect and no significant influence on MWC. IME may not have the inverse causal relationship with LV contractility that has been previously postulated but appears to have a direct causal association with diastolic stiffness as has been previously demonstrated.

Cardiac and peripheral failure in hemorrhagic shock in the dog

1964 ◽  
Vol 207 (1) ◽  
pp. 203-214 ◽  
Author(s):  
Carl F. Rothe ◽  
Ewald E. Selkurt
Keyword(s):  
Protein Concentration ◽  
Venous Pressure ◽  
Right Atrial ◽  
Cardiac Damage ◽  
Plasma Protein Concentration ◽  
Arterial Blood ◽  
Progressive Loss ◽  
Prolonged Hypotension ◽  
Pulmonary Arterial ◽  
Displacement Transducers

Cardiac output by the indocyanine-green-dilution technique, systemic arterial, right atrial, pulmonary arterial, and ventricular end-diastolic pressures were measured without thoracotomy to evaluate cardiac function in seven dogs. In other series of seven, mercury-in-rubber displacement transducers were placed around the left ventricles about 5 days before the experiments. In a third group of five, hemorrhagic hypotension was continued until 40% uptake of the maximum shed volume. Transfusions of blood, plasma, and dextran were given, as needed, to maintain arterial blood pressure above 100 mm Hg. Such therapy prolonged life. In a fourth group of 33, increases in hematocrit and plasma protein concentration, and decreases in central venous pressure suggested a progressive loss of intravascular fluid late in the hypotensive period and following transfusion. It appears that only with extreme degrees of oligemic hypotension, or with moderate hypotension plus prior cardiac damage does the cardiac weakness engendered by the prolonged hypotension become the most significant factor leading to death.

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