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N C Staub

Publications and source records attributed to N C Staub.

At least 55 records · Page 3Linked to original sources
PubMed1988

Lung microvascular pressure profile measured by micropuncture in anesthetized dogs.

We have micropunctured the lung in the open thorax of 17 anesthetized dogs to measure microvascular pressure. After intravenous pentobarbital sodium (25 mg/kg), we exposed the left lung through a wide left thoracotomy, which required rib excision. Through a double-lumen endotracheal tube, we ventilated the right lung to maintain normal blood gases and pH while we held the left lung motionless at an inflation pressure of 5 cmH2O. To reduce motion on the surface of the left lower lobe, we resected the left upper lobe, placed a Plexiglas baffle between the lobe and the heart, and held the lobe surface in a suction ring. In accordance with procedures we have previously described, we micropunctured subpleural vessels to measure microvascular pressure. At base line when alveolar pressure exceeded left atrial pressure (zone 2 conditions), 21, 38, and 41% of the total pressure drop occurred, respectively, in the arterial, microvascular, and venous segments. When we raised left atrial pressure above alveolar pressure (zone 3 conditions), the corresponding pressure drops were 30, 55, and 20% of total. The blood flow in the superficial layer of the lung averaged 15% less than the flow in the deeper layers as measured by distribution of 99mTc-albumin macroaggregates. We conclude that the intact and the isolated lung preparations in dog exhibit similar distributions of subpleural microvascular pressure.

Animals↗
PubMed1988

Equivalent pore estimate for the alveolar-airway barrier in isolated dog lung.

In high-pressure pulmonary edema, lung interstitial and air space edema liquids have equal protein concentrations (Am. J. Physiol. 231: 1466, 1976). This suggests that the alveolar-airway barrier separating the air and interstitial spaces is relatively unrestrictive, even without apparent epithelial injury. To estimate the equivalent pore population of the alveolar-airway barrier we inflated each of 18 isolated dog lung lobes for 1 h with a solution of colored tracer of uniform radius. Tracer radii ranged from 1.3 to 405 nm. After freezing the lobes in liquid N2, we measured interstitial tracer concentrations in frozen perivascular cuffs or in samples thawed after dissection from frozen cuffs. Relative to the concentrations instilled, interstitial concentrations ranged from 0.34 for the smallest particles (1.3 and 3.5 nm radius) to zero for particles with radii of 405 nm. From the results we designed a pore model of the alveolar-airway barrier to reproduce the concentrations we measured. No single-pore model could be obtained, although a three-pore model fit the data well. The model results predict that pores with radii of 1, 40, and 400 nm would account for 68, 30, and 2% of total liquid flux, respectively. The majority of liquid flux (68%) would occur through passageways smaller than the smallest tracer we used (1.3 nm radius). We believe the alveolar-airway barrier consists not only of tight intercellular junctions that allow passage of only water and electrolytes but also of a smaller number of large leaks that allow passage of particles up to nearly 400 nm in radius.

Animals↗
PubMed1988

Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep.

We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 mumol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24 +/- 2 to 55 +/- 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of less than 50 pg/ml to 250 +/- 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 mumol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 +/- 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that greater than 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.

Animals↗
PubMed1988

Effects of beta-adrenergic agents in lungs of normal and air-embolized awake sheep.

It is unclear whether beta-adrenergic agonists or antagonists affect lung liquid and protein exchange by changing pulmonary hemodynamics or microvascular leakiness. In 23 unanesthetized, instrumented sheep with long-term lung lymph fistulas, we assessed the effect of the beta-agonist terbutaline or the beta-antagonists propranolol, nadolol, and atenolol, all infused intravenously, on lung lymph flow under base-line conditions and during the acute lung injury caused by 4 h of venous air embolism. Under base-line conditions, neither beta-stimulation nor blockade had any effect. During air embolism, terbutaline decreased pulmonary vascular resistance and lymph flow by 25%. Propranolol and nadolol (non-selective beta 1,beta 2-antagonists) but not atenolol (selective beta 1-antagonist) also decreased lymph flow by 22% on average. We favor the more conservative (hemodynamic) over the more liberal (altered permeability) explanation for our results. First, beta-stimulation clearly caused vasodilation, which lowered the pulmonary microvascular pressure at the site of injury. beta-blockade caused changes similar to alpha-stimulation (J. Appl. Physiol. 62: 2147-2153, 1987). We therefore interpret the beta-blockade as unmasking pulmonary arterial alpha-receptors stimulated by the air-embolism injury, thus allowing vasoconstriction upstream to the site of injury. We do not believe the explanation of the beta-agent effects requires any modulation of lung microvascular leakiness by beta-adrenergic agents.

Adrenergic beta-Agonists↗
PubMed1988

Indirect estimate of perimicrovascular pressure rise in edema in isolated zone 1 lung.

To determine how liquid accumulation affects extra-alveolar perimicrovascular interstitial pressure, we measured filtration rate under zone 1 conditions (25 cmH2O alveolar pressure, 20 or 10 cmH2O vascular pressure) in isolated dog lung lobes in which all vessels were filled with autologous plasma. In the base-line condition, starting with normal extra-alveolar water content, filtration rate decreased by about one-half over 1 h as edema liquid slowly accumulated. We repeated each experiment after inducing edema (up to 100% lung weight gain). The absolute values and time course of filtration in the edema condition did not differ from base-line, i.e., the edema did not affect the time course of filtration. To compute the maximal initial and maximal change in extra-alveolar perimicrovascular pressure that occurred over each 1-h filtration study, we first assumed that the reflection coefficient is 0 in the Starling equation, then calculated perimicrovascular pressure and filtration coefficient from two equations with two unknowns. The mean filtration coefficient in 10 lobes is 0.063 g/(min X cmH2O X 100 g wet wt), and the initial perimicrovascular pressure is 3.9 cmH2O, rising by 4-7 cmH2O at 1 h. Finally we tested low protein perfusates and found the filtration rate was higher. We calculated an overall reflection coefficient = 0.44, a decrease in the initial perimicrovascular pressure to 1.9 cmH2O and a slightly lower increase after 1 h of edema formation, 2.2-6.6 cmH2O.

Algorithms↗
PubMed1988

Filtration profile in isolated zone 1 and zone 3 dog lungs at constant high alveolar pressure.

We measured the rate of liquid filtration in isolated dog lung lobes inflated to a constant alveolar pressure of 25 cmH2O and with all open vessels filled with plasma. We measured lung weight gain at vascular pressures ranging from 5 to 40 cmH2O relative to pleural pressure. We confirmed that under zone 1 conditions the "arterial" and "venous" extra-alveolar segments have essentially the same filtration characteristics. Using the combined extra-alveolar vascular system, we determined when recruitment of filtration surface area occurred as we increased vascular pressure from 0 to 40 cmH2O. Based on an abrupt increase in filtration rate as vascular pressure approached the zone 1/3 boundary, we infer that a sudden recruitment of exchange surface area occurred at that point. Based on the slopes of the zone 1 and zone 3 filtration profiles, we conclude that extra-alveolar vascular segments contribute approximately 25% of total to filtration in the lung under zone 3 conditions, although the exact vessels filtering under zone 1 conditions have yet to be determined. Our analysis of the data supports the concept that there is a difference in the perimicrovascular pressure around alveolar and extra-alveolar vessels, which in part may account for the apparent high filtration fraction apportioned to extra-alveolar vessels.

Animals↗
PubMed1988

Relationship of pleural effusions to increased permeability pulmonary edema in anesthetized sheep.

We studied anesthetized sheep to determine the relationship between increased permeability pulmonary edema and the development and mechanism of pleural effusion formation. In 12 sheep with intact, closed thoraces, we studied the time course of pleural liquid formation after 0.12 ml/kg i.v. oleic acid. After 1 h, there were no pleural effusions, even though extravascular lung water increased 50% to 6.0 +/- 0.7 g/g dry lung. By 3 h pleural effusions had formed, they reached a maximum at 5 h (48.5 +/- 16.9 ml/thorax), and at 8 h there was no additional accumulation of pleural liquid (45.5 +/- 16.9 ml). Morphologic studies by light and electron microscopy demonstrated subpleural edema but no detectable injury to the visceral pleura, suggesting that the pleural liquid originated from the lung and not the pleura. In nine sheep, we quantified the rate of formation of pleural liquid by enclosing one lung in a plastic bag. By comparing in the same sheep the volume of pleural liquid collected from the enclosed lung to the volume found in the opposite intact chest, we estimated the rate of liquid absorption from the intact chest to be 0.32 ml/(kg.h); we had previously reported a liquid absorption rate of 0.28 ml/(kg.h) in normal sheep. These studies also supported the conclusion that the majority of the pleural liquid originated from the lung because we could account for all of the pleural liquid that was formed and cleared. The volume of pleural liquid collected from the enclosed lungs was equal to 21% of the excess lung liquid that formed after oleic acid-induced lung injury. Thus, the pleural space and parietal pleural lymphatic pathways are important pathways for the clearance of pulmonary edema liquid after experimentally induced increased permeability pulmonary edema.

Animals↗
PubMed1987

Lung liquid and protein exchange: the four inhomogeneities.

William of Ockham, 14th-century scholastic philosopher at Oxford and Munich, emphasized the principle of economy, "pleurality is not to be supposed without necessity" (Ockham's razor). Necessity is the key word. In the modeling of steady-state lung liquid and protein exchange, the desire for simplicity has sometimes outweighed good judgment. In fact, we and others have shown that simple models do not work. It is necessary to include several forms of inhomogeneity. The air-filled lung shows regional (top to bottom) variations of mass, microvascular pressure, and perimicrovascular protein concentration. Normally, the small longitudinal (arterioles to venules) gradient of microvascular and perimicrovascular pressures is not a major concern, but in nonuniform disease processes, such as microembolism, longitudinal inhomogeneity, and parallel inhomogeneity are dominant. Multiple pores should also be considered a form of inhomogeneity. The effect on liquid and protein exchange, when plasma protein concentration or microvascular pressure change, can be readily explained using pore heterogeneity. The model I am currently using consists of a large number of discrete compartments (18), rather than a continuous distribution. We have recently identified a fifth inhomogeneity, which is that lung lymph flow might not always represent steady-state transvascular filtration because interstitial liquid may leak through the pleura or along the bronchovascular liquid cuffs into the mediastinum.

Blood Proteins↗
PubMed1987

Regional differences in pleural lymphatic albumin concentration in sheep.

We used quantitative reflectance autoradiography to compare the concentration of albumin in visceral pleural lymphatics at the cranial and caudal ends of the sheep's lung in the vertical (60 degrees head-up) and horizontal (supine) positions. Twelve to fourteen hours after injecting 125I-albumin intravenously we placed four anesthetized sheep in the vertical position to establish a microvascular hydrostatic pressure gradient along the vertical height of the lung. We placed two anesthetized sheep in the horizontal position. Four hours later, we fixed the left lung and removed visceral pleural tissue blocks from the cranial and caudal ends, separated by a 15-cm distance, along the costovertebral margin. We measured the silver grain density in the pleural lymphatic autoradiograms by dark-field reflectance microspectrophotometry. In the vertical position, the lymph albumin concentration at the cranial end (top) of the lung averaged 2.5 +/- 0.4 g/dl compared with the caudal end (bottom), which averaged 1.8 +/- 0.3 g/dl. The difference (42% greater at the top than the bottom) is significant (P less than 0.05). The computed gradient in perimicrovascular interstitial albumin osmotic pressure was 0.26 +/- 0.13 cmH2O/cm lung height. There were no differences between the cranial and caudal lymphatic groups in the two horizontal sheep. We conclude that in the sheep lung there is a gradient in perimicrovascular albumin concentration due to the vertical gradient in microvascular hydrostatic pressure.

Albumins↗
PubMed1987

Does interstitial lung edema compress airways and arteries? A morphometric study.

We compared areas and diameters of small airways and arteries in three groups of anesthetized dogs: 1) control (n = 5), 2) hydrostatic edema induced by fluid overload (n = 13), and 3) increased permeability edema induced with alpha-naphthylthiourea (n = 5). We measured pulmonary arterial and wedge pressures in all groups and cardiac output in the hydrostatic edema group. Postmortem, lobes were frozen at functional residual capacity and samples taken for measurements of extravascular lung water (Qwl/dQl) and for light microscopy. We also examined lobes from hydrostatic edema experiments fixed at transpulmonary pressures of 5 and 27 cmH2O. From the histology slides, bronchovascular bundles with respiratory bronchioles (n = 706) and bronchioles (n = 467) were photographed and airway and vessel areas and diameters measured. Alveolar and airway luminal edema were graded. We found that only in hydrostatic edema, pulmonary arterial and wedge pressures increased and vascular resistance fell with fluid infusion. Mean Qwl/dQl values were 3.80 +/- 0.17, 6.81 +/- 0.96, and 9.34 +/- 0.62 (SE) in control, hydrostatic, and increased permeability edema groups, respectively. By quantitative histology, airway and arterial areas and diameters did not decrease in edema and rose with increasing transpulmonary pressure. Variable quantities of air-space edema were seen. We conclude that interstitial edema does not compress small airways or arteries and that other mechanisms, including alveolar and airway luminal edema, may explain reported increases in airway resistance.

Animals↗
PubMed1987

Liquid thickness vs. vertical pressure gradient in a model of the pleural space.

In recent studies using relatively noninvasive techniques, the vertical gradient in pleural liquid pressure was 0.2-0.5 cmH2O/cm ht, depending on body position, and pleural liquid pressure closely approximated lung recoil (J. Appl. Physiol. 59: 597-602, 1985). We built a model to discover why the vertical gradient in pleural pressure is less than hydrostatic (1 cmH2O/cm). A long rubber balloon of cylindrical shape was inflated in a plastic cylinder. The "pleural" space between the balloon and cylinder was filled with blue-dyed water. With the cylinder vertical, we measured pleural pressure by a transducer through side taps at 2-cm intervals up the cylinder. The pressure was measured with different amounts of water in the pleural space. With a clear separation between the balloon and the container, the vertical gradient in pleural liquid pressure was hydrostatic. As water was withdrawn from the pleural space, the balloon approached the wall of the container. Over an 8-cm-long midregion of the model where the balloon diameter matched the cylinder diameter, the vertical gradient was not hydrostatic and was virtually absent. In this region, the pleural liquid pressure was uniform and equal to the recoil of the balloon. In this section we could not see any pleural space. By scintillation imaging using 99mTc-diethylenetriamine pentaacetic acid in the water, we estimated the thickness of this flat "costal" pleural space to be approximately 20 microns. Radioactive tracer injected at the top of the pleural space appeared by 24 h at the bottom, which indicated a slow drainage of liquid by gravity.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Fluids↗
PubMed1987

Alpha-adrenergic agents have little effect during air embolism lung injury in awake sheep.

Since it is not clear whether alpha-adrenergic receptors can modulate lung microvascular liquid and protein leakiness, we studied the effects of alpha-adrenergic receptor stimulation or blockade on lung filtration under base-line conditions and during the acute lung injury caused by a 4-h infusion of venous air emboli in six unanesthetized, chronically instrumented sheep with lung lymph fistulas. During the experiments we continuously infused the alpha-adrenergic receptor agonist phenylephrine hydrochloride (1.0 microgram X kg-1 X min-1 iv) or the alpha-adrenergic receptor antagonist phentolamine mesylate (1.0 mg X kg-1 X min-1 iv), and we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and the lymph-to-plasma protein concentration ratio. During air embolism, alpha-receptor stimulation increased pulmonary vascular resistance and decreased lung lymph flow by 25%; alpha-receptor blockade had the opposite effects. During recovery, neither agent significantly affected pulmonary hemodynamics or lymph flow. Our results indicate that alpha-adrenergic receptors are active during air embolism and modulate pulmonary filtration by causing arteriolar constriction, which reduces the surface area or the perfusion pressure in the pulmonary microvascular bed. They may also affect venous smooth muscle tone. We found no evidence that alpha-adrenergic receptors modulate lung microvascular liquid or protein leakiness directly.

Animals↗
PubMed1987

No gravity-independent gradient of blood flow distribution in dog lung.

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.

Animals↗
PubMed1987

Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep.

We did experiments to determine whether beta-adrenergic agonists increase lung liquid clearance in anesthetized ventilated adult sheep and, if so, whether the increase is mediated by beta receptors and what mechanism is involved. We instilled 100 ml of autologous serum either alone or with a beta-adrenergic agonist (terbutaline, 10(-5) M, or epinephrine, 5.5 X 10(-6) M) into one lower lobe. After 4 h both terbutaline and epinephrine increased lung liquid clearance. The increase in lung liquid clearance was inhibited when propranolol (a beta blocker) or amiloride (a sodium channel blocker) was added to the terbutaline. Increased clearance was not explained by changes in pulmonary hemodynamics, pulmonary blood flow, or lung lymph flow. We conclude that beta-adrenergic agonists increase lung liquid clearance in anesthetized intact adult sheep. This increase is mediated through beta receptors and probably depends on increased active transport of sodium across the alveolar barrier.

Adrenergic beta-Agonists↗
PubMed1986

Vascular tracers alter hemodynamics and airway pressure in anesthetized sheep.

The technique of vascular labeling was developed to mark sites of increased microvascular permeability. We used the vascular labeling technique in anesthetized sheep and found that hemodynamics and airway pressure were adversely affected by intraarterial infusions of two vascular tracers. Monastral blue (nine sheep) immediately caused systemic arterial hypotension, pulmonary arterial hypertension, and bronchoconstriction. All three physiological responses were partially blocked by a cyclooxygenase inhibitor (indomethacin) but not by an H1-antihistamine (chlorpheniramine). Colloidal gold (nine sheep) caused immediate, but less dramatic, pulmonary arterial hypertension which was not attenuated by the blocking agents. We conclude that these two vascular tracers caused detrimental physiological side effects in sheep at the usual doses used to label injured microvessels in other species.

Animals↗
PubMed1986

Intrathoracic sources of caudal mediastinal lymph node efferent lymph in sheep.

We investigated the intrathoracic contributions to the caudal mediastinal lymph node (CMN) efferent lymph in 12 anesthetized sheep after removing possible systemic contributions from below the diaphragm. We interrupted various pathways that may send lymph to the CMN (chest wall, esophagus, lung). Because the experiment is destructive, we did the resections in various combinations and waited 1 h between steps. Base-line CMN efferent lymph flow averaged 0.90 +/- 0.52 g/15 min (mean +/- SD). Cutting the pulmonary ligaments bilaterally caused lymph flow to decrease by an average of 58%. In five sheep, cauterizing around the lung hila reduced lymph flow by 16% of base line, cauterizing along the esophagus reduced lymph flow by 18% of base line, and cauterizing along the chest wall increased lymph flow by 6% of base line. After complete isolation of the node, except for the bronchoesophageal artery, dorsal mediastinal vein, and CMN efferent duct, 14% of base-line flow remained. The lymph-to-plasma total protein concentration ratios did not change significantly with any procedure. Under the conditions of our experiments, approximately 74% of base-line intrathoracic CMN efferent flow comes from the lung.

Abdominal Muscles↗