PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat

2001 ◽  
Vol 90 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Leonardo C. Clavijo ◽  
Mary B. Carter ◽  
Paul J. Matheson ◽  
Mark A. Wilson ◽  
William B. Wead ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Ex Vivo ◽  
Platelet Activating Factor ◽  
Microvascular Permeability ◽  
Blue Dye ◽  
E Coli ◽  
Pulmonary Arterial

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.

Flow through zone 1 lungs utilizes alveolar corner vessels

1991 ◽  
Vol 70 (4) ◽  
pp. 1518-1523 ◽  
Author(s):  
W. J. Lamm ◽  
K. R. Kirk ◽  
W. L. Hanson ◽  
W. W. Wagner ◽  
R. K. Albert
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Left Lung ◽  
Lateral Position ◽  
Double Lumen Endotracheal Tube ◽  
Mean Pulmonary Arterial Pressure ◽  
Flow Through ◽  
Pulmonary Arterial ◽  
Isolated Lungs

We have previously observed flows equivalent to 15% of the resting cardiac output of rabbits occurring through isolated lungs that were completely in zone 1. To distinguish between alveolar corner vessels and alveolar septal vessels as a possible zone 1 pathway, we made in vivo microscopic observations of the subpleural alveolar capillaries in five anesthetized dogs. Videomicroscopic recordings were made via a transparent thoracic window with the animal in the right lateral position. From recordings of the uppermost surface of the left lung, alveolar septal and corner vessels were classified depending on whether they were located within or between alveoli, respectively. Observations were made with various levels of positive end-expiratory pressure (PEEP) applied only to the left lung via a double-lumen endotracheal tube. Consistent with convention, flow through septal vessels stopped when PEEP was raised to the mean pulmonary arterial pressure (the zone 1-zone 2 border). However, flow through alveolar corner vessels continued until PEEP was 8-16 cmH2O greater than mean pulmonary arterial pressure (8-16 cm into zone 1). These direct observations support the idea that alveolar corner vessels rather than patent septal vessels provide the pathway for blood flow under zone 1 conditions.

Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury

1994 ◽  
Vol 77 (2) ◽  
pp. 888-895 ◽  
Author(s):  
S. P. Janssens ◽  
S. W. Musto ◽  
W. G. Hutchison ◽  
C. Spence ◽  
M. Witten ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Weight Ratio ◽  
Peak Inspiratory Pressure ◽  
Dry Weight ◽  
Lymph Flow ◽  
Pulmonary Arterial ◽  
Arterial Po2

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.

A canine model of neurogenic pulmonary edema

1985 ◽  
Vol 59 (3) ◽  
pp. 1019-1025 ◽  
Author(s):  
M. B. Maron
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Canine Model ◽  
Systemic Arterial Pressure ◽  
Left Ventricular ◽  
Neurogenic Pulmonary Edema ◽  
Lung Water ◽  
Pulmonary Arterial ◽  
Alpha Chloralose

The purpose of this study was to evaluate the usefulness of the intracisternal administration of veratrine as a model of neurogenic pulmonary edema (NPE) in the alpha-chloralose-anesthetized dog. Veratrine (40–60 micrograms/kg) was injected into the cisterna magna of 17 animals, and systemic arterial, pulmonary arterial, and left ventricular end-diastolic (LVEDP) pressures were followed for 1 h. Eleven animals developed alveolar edema. In these animals, systemic arterial pressure increased to 273 +/- 9 (SE) Torr, pulmonary arterial pressure to 74.5 +/- 4.9 Torr, and LVEDP to 42.8 +/- 4.5 Torr, and large amounts of pink frothy fluid, with protein concentrations ranging from 48 to 93% of plasma, appeared in the airways. Postmortem extravascular lung water content (Qwl/dQl) averaged 7.30 +/- 0.46 g H2O/g dry lung wt. Six animals escaped developing this massive degree of edema after veratrine (Qwl/dQl = 4.45 +/- 0.24). These animals exhibited similar elevated systemic arterial pressures (268 +/- 15 Torr), but did not develop the degree of pulmonary hypertension (pulmonary arterial pressure = 52.5 +/- 6.7 Torr, LVEDP = 24.8 +/- 4.0 Torr) observed in the other group. These results suggest that both hemodynamic and permeability mechanisms may play a role in the development of this form of edema and that veratrine administration may provide a useful model of NPE.

A New Look at Pulmonary Edema

Physiology ◽  
1986 ◽  
Vol 1 (5) ◽  
pp. 150-153 ◽  
Author(s):  
GA Laine ◽  
SJ Allen ◽  
JP Williams ◽  
J Katz ◽  
JC Gabel ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Critically Ill Patients ◽  
Pulmonary Arterial Pressure ◽  
Venous Pressure ◽  
Colloid Osmotic Pressure ◽  
Fluid Accumulation ◽  
Fatal Complication ◽  
Therapeutic Measures ◽  
Pulmonary Arterial

Fluid accumulation within the lungs is a potentially fatal complication in critically ill patients. Sepsis and increased microvascular permeability are often implicated as the cause. This article shows that edema can be prevented by lowering systemic venous pressure (to permit pulmonary lymph to drain), by lowering pulmonary arterial pressure, and by maintaining plasma colloid osmotic pressure. It points out the importance of understanding the basic physiology behind pulmonary edema and therapeutic measures.

Fetal pulmonary vasodilation after exogenous platelet-activating factor

1991 ◽  
Vol 70 (2) ◽  
pp. 778-787 ◽  
Author(s):  
F. J. Accurso ◽  
S. H. Abman ◽  
R. B. Wilkening ◽  
G. S. Worthen ◽  
P. Henson
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Ductus Arteriosus ◽  
Platelet Activating Factor ◽  
Vena Cava ◽  
Arterial Blood Flow ◽  
High Dose ◽  
Pulmonary Vasodilation ◽  
Arterial Blood ◽  
Pulmonary Arterial

To determine the fetal pulmonary vascular response to platelet-activating factor (PAF), we studied the hemodynamic effects of the infusion of PAF directly into the left pulmonary artery in 21 chronically catheterized fetal lambs. Left pulmonary arterial blood flow (Q) was measured with electromagnetic flow transducers. Ten-minute infusions of low-dose PAF (10-100 ng/min) produced increases in Q from a baseline of 71 +/- 5 to 207 +/- 20 ml/min (P less than 0.001) without changes in pulmonary arterial pressure. Pulmonary vasodilation with PAF was further confirmed through increases in Q with brief (15-s) infusions and increases in the slope of the pressure-flow relationship as assessed by rapid incremental compressions of the ductus arteriosus during PAF infusion. Infusion of Lyso-PAF had no effect on Q or pulmonary arterial pressure. Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone. Systemic infusion of high-dose PAF (300 ng/min) through the fetal inferior vena cava increased pulmonary arterial pressure (46.5 +/- 1.0 to 54.8 +/- 1.9 mmHg, P less than 0.01) and aorta pressure (44.3 +/- 1.0 to 52.7 +/- 2.2 mmHg, P less than 0.01) while also increasing Q. Neither PAF nor CV-3988 changed the gradient between pulmonary arterial and aorta pressures, suggesting that PAF does not affect ductal tone. We conclude that PAF is a potent fetal pulmonary vasodilator and that the effects are not mediated through cyclooxygenase products or by cholinergic or histaminergic effects.

Effects of lung inflation on pulmonary arterial pressure in dogs with pulmonary edema

1978 ◽  
Vol 45 (3) ◽  
pp. 442-450 ◽  
Author(s):  
J. F. Murray
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Base Line ◽  
Lung Volumes ◽  
Lung Inflation ◽  
Trapped Air ◽  
Pulmonary Arterial ◽  
The Right ◽  
Line Zone

The effects of lung inflation from positive airway pressure (Paw) on pulmonary arterial pressure (Ppa) and the slope deltaPpa/deltaPaw were studied in normal dogs and dogs with pulmonary edema. Under base-line zone 2 conditions with the lungs perfused at constant flow (100 ml/kg per min) and vascular pressures measured relative to pleural (atmospheric) pressure, the slope deltaPpa/deltaPaw was nearly one (at Paw greater than or equal to 5 cmH2O). Pulmonary edema from high capillary pressure and oleic acid caused deltaPpa/deltaPaw and Ppa to decrease at high lung volumes and Ppa to increase at low lung volumes. These changes were not simulated by vasoactive drugs (adenosine and norepinephrine) but were reproduced by instilling dextran into the lungs and, in part, by occluding the right intermediate bronchus. In pulmonary edema the increased Ppa at low lung volumes is caused by the effects of decreases in the caliber of extra-alveolar vessels, by trapped air or liquid raising alveolar pressure, or by both; the decreased deltaPpa/deltaPaw and Ppa at high volumes is caused mainly by nonuniform distribution of driving pressures and blood flow.

A novel right-heart catheterization technique for in vivo measurement of vascular responses in lungs of intact mice

2000 ◽  
Vol 278 (1) ◽  
pp. H8-H15 ◽  
Author(s):  
Hunter C. Champion ◽  
Douglas J. Villnave ◽  
Allen Tower ◽  
Philip J. Kadowitz ◽  
Albert L. Hyman
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Right Heart ◽  
Catheterization Technique ◽  
Pulmonary Arterial ◽  
The Right ◽  
Spontaneously Breathing

The present study employed a new right-heart catheterization technique to measure pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary vascular resistance in anesthetized intact-chest, spontaneously breathing mice. Under fluoroscopic guidance, a specially designed catheter was inserted via the right jugular vein and advanced to the main pulmonary artery. Cardiac output was determined by the thermodilution technique, and measured parameters were stable for periods of ≤3 h. Pressure-flow curves in vivo were curvilinear, with mean pulmonary arterial pressure increasing more rapidly at low pulmonary blood flows of 5–10 ml/min and less rapidly at higher blood flow rates. The pressure-flow relationship was shifted to the left by the nitric oxide synthase inhibitor nitro-l-arginine methyl ester (l-NAME) at higher blood flow levels, whereas the cyclooxygenase inhibitor sodium meclofenamate was without effect. The increase in pulmonary arterial pressure in response to acute hypoxia (fractional inspired O2 10%) was augmented byl-NAME but unaltered by sodium meclofenamate. The present results demonstrate that the right-heart catheterization technique can be used to measure pulmonary vascular pressures and responses in the mouse. This is, to our knowledge, the first report of a right-heart catheterization technique to measure pulmonary vascular pressures and responses in the intact-chest, spontaneously breathing mouse and should prove useful for the investigation of pulmonary vascular responses in transgenic mice.

Pulmonary responses to phospholipase A2 in the perfused guinea pig lung

1989 ◽  
Vol 67 (6) ◽  
pp. 2495-2503 ◽  
Author(s):  
W. M. Selig ◽  
S. K. Durham ◽  
A. F. Welton
Keyword(s):  
Arterial Pressure ◽  
Guinea Pig ◽  
Phospholipase A2 ◽  
Receptor Antagonist ◽  
Pulmonary Arterial Pressure ◽  
Platelet Activating Factor ◽  
Lung Weight ◽  
Fluid Filtration ◽  
Airway Constriction ◽  
Pulmonary Arterial

We examined the effect of phospholipase A2 (PLA2; Naja naja) challenge on pulmonary hemodynamics, airway constriction, and fluid filtration in isolated Ringer-perfused guinea pig lungs. Intratracheal PLA2 (10-100 U) produced dose-dependent increases in pulmonary arterial pressure, intratracheal pressure, and lung weight, although intravenous PLA2 administration had no effect on monitored variables. Morphological features indicative of airway constriction and pulmonary edema were observed by light microscopy. PLA2-induced increases in intratracheal pressure and/or lung weight were attenuated to varying degrees by pretreatment with indomethacin (1 microM, a cyclooxygenase inhibitor), ICI-198,615 (1 microM, a leukotriene D4 receptor antagonist), and WEB 2086 (1 microM, a platelet-activating factor antagonist). PLA2-induced increases in pulmonary arterial pressure and intratracheal pressure were also reduced in lungs removed from animals pretreated with dexamethasone (50 mg/kg ip for 2 days; a steroidal antiinflammatory agent). Pyrilamine (1 microM, a histamine1-receptor antagonist) and Takeda AA861 (1 microM, a delta 5-lipoxygenase inhibitor) did not produce significant inhibitory effects on PLA2-induced pathophysiological changes. Intratracheal instillation of high-dose platelet-activating factor (50 micrograms) or lysophosphatidylcholine (100 micrograms) produced gradual increases in intratracheal pressure and lung weight, but these changes were not as large as those induced by PLA2. Thus these studies suggest that resident cell populations associated with airways may play an important role in PLA2-induced pathophysiological changes in the perfused guinea pig lung. These PLA2-induced effects are most likely partially mediated by generation of eicosanoids and platelet-activating factor.

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