Effect of blood and albumin on pulmonary hypertension and edema in perfused rabbit lungs

1995 ◽  
Vol 78 (2) ◽  
pp. 499-504 ◽  
Author(s):  
S. A. Kraft ◽  
S. Fujishima ◽  
G. P. McGuire ◽  
J. S. Thompson ◽  
T. A. Raffin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Edema ◽  
Nitrogen Mustard ◽  
Blood Perfusion ◽  
Leukocyte Activation ◽  
Buffer Solution ◽  
Edema Formation ◽  
Pulmonary Hemodynamics ◽  
Buffer Solutions ◽  
Macromolecular Permeability

Perfusate composition may alter pulmonary hemodynamics and edema formation in perfused lungs. Perfusion for 3 h with Krebs-Henseleit solution with 3% bovine serum albumin did not produce pulmonary hypertension, pulmonary edema (assessed by lung wet-to-dry wt ratio), or increased macromolecular permeability (assessed by 125I-albumin uptake). Addition of blood to hematocrit levels of 10 or 20% resulted in pulmonary hypertension during the final hour of perfusion but not pulmonary edema or increased macromolecular permeability. Pulmonary hypertension during blood perfusion was primarily due to increased precapillary resistance. Perfusion with buffer solution without albumin produced edema and increased macromolecular permeability but not pulmonary hypertension. In lungs perfused with blood (20% hematocrit), thromboxane B2 levels increased in parallel with the pulmonary hypertension, and inhibition of cyclooxygenase or thromboxane synthase with indomethacin or dazmegrel prevented pulmonary hypertension. Perfusion with leukopenic blood (from prior nitrogen mustard administration or from filtration) also prevented pulmonary hypertension. We conclude that blood perfusion produces pulmonary hypertension via thromboxane A2 generation, which depends on leukocyte activation, and that perfusion with buffer solutions without albumin produces edema and increased permeability without pulmonary hypertension.

scholarly journals Oxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 155
Author(s):  
Daniel Morales-Cano ◽  
Bianca Barreira ◽  
Beatriz De Olaiz Navarro ◽  
María Callejo ◽  
Gema Mondejar-Parreño ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Pulmonary Circulation ◽  
Pulmonary Arteries ◽  
Blood Perfusion ◽  
Mesenteric Arteries ◽  
Oxygen Sensitivity ◽  
Low Oxygen ◽  
Oxygen Selectivity

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.

Mechanisms leading to lung edema in pulmonary embolization

1960 ◽  
Vol 198 (3) ◽  
pp. 543-546 ◽  
Author(s):  
S. A. Kabins ◽  
J. Fridman ◽  
J. Neustadt ◽  
G. Espinosa ◽  
L. N. Katz
Keyword(s):  
Pulmonary Edema ◽  
Capillary Permeability ◽  
Lysergic Acid ◽  
Lung Edema ◽  
Pulmonary Infarction ◽  
Edema Formation ◽  
Lung Lobe ◽  
Pulmonary Embolization ◽  
Sympathetic Nervous ◽  
Lung Lobes

A localized pulmonary infarction was produced by injecting a starch suspension into the pulmonary artery wedge position of one lung lobe in pentobarbitalized dogs, and the effect of three so-called antiserotonins on the ensuing pulmonary edema was determined. Edema was inhibited in the nonembolized lung lobes in 88% of the B.A.S. (1-benzyl-2-methyl-5-methoxytryptamine HCl), 45% of the DHE (dihydroergotamine), and 12% of the BOL (2-brom- d-lysergic acid diethylamide) dogs. Reasons are given for assuming that the actions of B.A.S. and DHE are due to their antiadrenergic rather than to any antiserotonin properties which they may have. Serotonin, therefore, at most has a slight role in the pulmonary edema formation caused by starch emboli. It is postulated that the emboli by producing an infarct and setting up a reflex mediated through the sympathetic nervous system, cause the release in turn of catecholamines and of histamine, the latter being immediately responsible for the capillary permeability change leading to pulmonary edema.

Rumination in sheep. III. Experimentally induced variations on the circadian pattern of rumination

1965 ◽  
Vol 16 (4) ◽  
pp. 649 ◽  
Author(s):  
GR Pearce
Keyword(s):  
Extended Period ◽  
High Protein ◽  
Circadian Pattern ◽  
Buffer Solution ◽  
Buffer Solutions ◽  
Experimentally Induced

The circadian (24-hr) pattern of rumination of caged sheep was found to be affected: (a) by the administration of a roughage ration per fistulam; (b) by the emptying of the rumen and the subsequent return of the rumen contents; (c) by the emptying of the rumen and the replacement of the contents by a buffer solution plus roughage. The period during which no rumination occurred following feeding was progressively shortened when increasing proportions of a ration of oaten chaff and lucerne chaff were administered per fistulam. The effect was much reduced when high protein sheep cubes were added to the chaff ration. The removal of the rumen contents after voluntary feeding and then their immediate return to the rumen tended to cause an early commencement of rumination. When the rumen contents were "pasteurized" before return, however, rumination did not occur for an extended period afterwards. When the rumen contents were replaced with buffer solutions plus roughage, variable rumination responses occurred. In one instance apparently uninhibited rumination resulted.

scholarly journals ULTRACENTRIFUGATION STUDIES ON THE ELEMENTARY BODIES OF VACCINE VIRUS

1938 ◽  
Vol 68 (4) ◽  
pp. 607-627 ◽  
Author(s):  
Joseph E. Smadel ◽  
Edward G. Pickels ◽  
Theodore Shedlovsky
Keyword(s):  
Sedimentation Rate ◽  
Vaccine Virus ◽  
Normal Rate ◽  
Buffer Solution ◽  
Buffer Solutions ◽  
Original Volume ◽  
Sucrose Solutions ◽  
Rate Of Sedimentation

Ultracentrifugal studies of the CL dermal strain of vaccine virus warrant the following conclusions: 1. When suspended in increasing concentrations of sucrose, glycerol, or urea solutions, elementary bodies of vaccinia show variations in sedimentation rate which indicate changes in the density or size of the particles. For a given change in the density of the medium these changes are smallest with sucrose and most marked with urea. The normal rate of sedimentation of Paschen bodies may be restored by resuspending them in dilute buffer solution. 2. The density of elementary bodies of vaccinia suspended in dilute buffer solutions is estimated to be 1.16 gm. per cc. Higher values for the density are found if the particles are suspended in solutions containing sucrose, glycerol, or urea. In 53 per cent sucrose, for example, the density is 1.25 gm. per cc. 3. Paschen bodies appear to be quite permeable to water and urea, less so to glycerol, and only slightly, if at all, to sucrose. 4. The increased density of the elementary bodies of vaccinia in sucrose solutions may be accounted for by an osmotic extraction of water from the particles. On this basis the water which can be thus extracted corresponds to at least a third of the original volume of the particles.

scholarly journals Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

2013 ◽  
Vol 304 (12) ◽  
pp. L894-L901 ◽  
Author(s):  
Cassidy Delaney ◽  
Jason Gien ◽  
Gates Roe ◽  
Nicole Isenberg ◽  
Jenai Kailey ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Tryptophan Hydroxylase ◽  
Late Gestation ◽  
Persistent Pulmonary Hypertension ◽  
Sheep Model ◽  
Pulmonary Hemodynamics ◽  
Fetal Sheep ◽  
Pulmonary Arterial

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment ( P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment ( P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment ( P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model.

Alpha-thrombin-induced pulmonary vasoconstriction

1987 ◽  
Vol 63 (5) ◽  
pp. 1993-2000 ◽  
Author(s):  
M. J. Horgan ◽  
J. W. Fenton ◽  
A. B. Malik
Keyword(s):  
Pulmonary Edema ◽  
Base Line ◽  
Thrombin Injection ◽  
Weight Changes ◽  
Lung Weight ◽  
Edema Formation ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Hemodynamic ◽  
Proteolytic Site ◽  
Synthase Inhibitor

We examined the direct effects of thrombin on pulmonary vasomotor tone in isolated guinea pig lungs perfused with Ringer albumin (0.5% g/100 ml). The injection of alpha-thrombin (the native enzyme) resulted in rapid dose-dependent increases in pulmonary arterial pressure (Ppa) and pulmonary capillary pressure (Ppc), which were associated with an increase in the lung effluent thromboxane B2 concentration. The Ppa and Ppc responses decreased with time but then increased again within 40 min after thrombin injection. The increases in Ppc were primarily the result of postcapillary vasoconstriction. Pulmonary edema as evidenced by marked increases (60% from base line) in lung weight occurred within 90 min after thrombin injection. Injection of modified thrombins (i.e., gamma-thrombin lacking the fibrinogen recognition site or i-Pr2P-alpha-thrombin lacking the serine proteolytic site) was not associated with pulmonary hemodynamic or weight changes nor did they block the effects of alpha-thrombin. Indomethacin (a cyclooxygenase inhibitor), dazoxiben (a thromboxane synthase inhibitor), or hirudin (a thrombin antagonist) inhibited the thrombin-induced pulmonary vasoconstriction, as well as the pulmonary edema. We conclude that thrombin-induced pulmonary vasoconstriction is primarily the result of constriction of postcapillary vessels, and the response is mediated by generation of cyclooxygenase-derived metabolites. The edema formation is also dependent on activation of the cyclooxygenase pathway. The proteolytic site of alpha-thrombin is required for the pulmonary vasoconstrictor and edemogenic responses.

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%).

Effects of pulmonary edema on regional pulmonary perfusion in the intact dog lung

1980 ◽  
Vol 49 (5) ◽  
pp. 834-840 ◽  
Author(s):  
A. B. Malik ◽  
H. van der Zee ◽  
P. H. Neumann ◽  
N. B. Gertzberg
Keyword(s):  
Blood Flow ◽  
Pulmonary Edema ◽  
Pulmonary Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Weight Ratio ◽  
Flow Distribution ◽  
Base Line ◽  
Dependent Lung ◽  
Lung Water ◽  
Pulmonary Hemodynamics

Regional pulmonary blood flow was determined in dogs during varying degrees of pulmonary edema induced by infusing 179.2-659.4 ml/kg normal saline over 2-3 h. Pulmonary hemodynamics and regional blood flows were measured during the base-line period and at 30 min postinfusion. The degree of pulmonary edema was determined by the final extravascular lung water-to-bloodless dry lung weight ratio (W/D). In dogs developing gross alveolar edema (W/D of 10.70 +/- 0.88 vs. 3.10 +/- 0.30 in controls), the blood flow was shifted to either upper or dependent lung regions. The shift to the upper regions was associated with an increased (P < 0.05) pulmonary arterial pressure (Ppa), whereas the shift to the dependent lung was not associated with a significant change in Ppa. Breathing 100% O2 did not prevent these shifts, suggesting that they were not due to localized hypoxic pulmonary vasoconstriction. The flow distribution patterns were also not related to regional differences in edema. In contrast to the changes during fulminant edema, blood flow distribution did not change after moderate levels of pulmonary edema (W/D of 6.03 0.69), suggesting that gross alveolar flooding is required for a redistribution of pulmonary blood flow. Flow redistribution to the upper lung during airway flooding may be due to increase in Ppa, whereas the increased flow in the dependent lung during the same degree of edema may be due to "bulging" of alveolar vessels into the air spaces, secondary to a decrease in surface activity.

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