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N C Staub

Publications and source records attributed to N C Staub.

At least 37 records · Page 2Linked to original sources
PubMed1991

No evidence for mesothelial cell contact across the costal pleural space of sheep.

Pleural space width was measured by four morphological approaches using either frozen hydrated or freeze-substituted blocks of chest wall and lung. Anesthetized sheep were held in the lateral (n = 2), sternal recumbent (n = 2), or vertical (head-up; n = 2) position for 30 min. The ribs and intercostal muscles were excised along a 20-cm vertical distance of the chest wall region, which was sprayed with liquid Freon 22, cooled with liquid nitrogen, to facilitate the fastest possible freezing of the visceral and parietal pleura. We measured pleural space width in frozen hydrated blocks by reflected-light and low-temperature scanning electron microscopy and in freeze-substituted, fixed, and embedded tissue blocks by light and transmission electron microscopy. We combined the data from the two groups of sheep held sternally recumbent and vertical because the results were comparable. The average arithmetic mean data for pleural space width determined by reflected-light analysis for samples near the top (18.5 microns) and bottom (20.3 microns) of the chest, separated by 15 cm of lung height, varied inversely with lung height (n = 4; P less than 0.009). The average harmonic mean data demonstrated a similar gravity-dependent gradient (17.3 and 18.8 microns, respectively; P less than 0.02). Therefore a slight vertical gradient of approximately -0.10 micron/cm of lung height was found for costal pleural space width. Pleural space width in the most dependent recesses, such as the costodiaphragmatic recess, reached 1-2 mm. We never found any contacts between the visceral and parietal pleura with either of the frozen hydrated preparations. No points of mesothelial cell contact were revealed in the light- and transmission electron microscopic views of the freeze-substituted tissue, despite an apparent narrower pleural space associated with the tissue-processing steps. We conclude that the pleural space has a slightly nonuniform width, contacts if they occur must be very infrequent, and pleural liquid clearance is probably facilitated by liquid accumulation in dependent regions where lymphatic pathways exist.

Animals↗
PubMed1991

Plasma protein osmotic pressure equations and nomogram for sheep.

The equations developed by Landis and Pappenheimer (Handbook of Physiology. Circulation, 1963, p. 961-1034) for calculating the protein osmotic pressure of human plasma proteins have been frequently used for other animal species without regard to the fractional albumin concentration or correction for protein-protein interaction. Using an electronic osmometer, we remeasured the protein osmotic pressure of purified sheep albumin and sheep plasma partially depleted of albumin. We measured protein osmotic pressures of serial dilutions over the concentration range 0-180 g/l for albumin and 0-100 g/l for the albumin-depleted proteins at room temperature (26 degrees C). Using a nonlinear least squares parameter-fitting computer program, we obtained the equation of best fit for purified albumin, and then we used that equation together with the measured albumin fraction to obtain the best-fit equation for the nonalbumin proteins. The equation for albumin is IIcmH2O,39 degrees C = 0.382C + 0.0028C2 + 0.000013C3, where C is albumin concentration in g/l. The equation for the nonalbumin fraction is IIcmH2O,39 degrees C = 0.119C + 0.0016C2. Up to 200- and 100-g/l protein concentration, respectively, these equations give the least standard error of the estimate for each of the virial coefficients. The computed number-average molecular weight for the nonalbumin proteins is 222,000. Using the new equations, we constructed a nomogram, based on the one of Nitta and co-workers (Tohoku J. Exp. Med. 135: 43-49, 1981). We tested the nomogram using 144 random samples of sheep plasma and lymph from 31 sheep. We obtained a correlation coefficient of 0.99 between the measured and nomogram estimates of protein osmotic pressure.

Animals↗
PubMed1991

Effect of catheter size on pressures recorded in small pulmonary veins in dog lung.

Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions.

Animals↗
PubMed1991

Pulmonary hemodynamic reaction to foreign blood in goats and rabbits.

We have found that the goat is extraordinarily sensitive to very small quantities of rabbit or rat blood. As little as 0.004 ml/kg induces transient pulmonary hypertension [maximal rise in pulmonary arterial pressure 32 +/- 10 (SD) cmH2O] in goats. We hypothesized that this reaction may be related to the presence of the resident population of intravascular macrophages that reside in the pulmonary capillaries of goats. If that is so, then rabbits or rats, which have few or no intravascular macrophages, should not be reactive to foreign blood. We compared pulmonary hemodynamics and changes in blood thromboxane B2 concentrations among goats, rabbits, and rats in response to graded doses of foreign blood. The pulmonary reaction to foreign blood was much greater in goats than in rabbits or rats, even though we injected up to 10- or 60-fold larger amounts into the latter species. In goats the pulmonary vascular pressure response to rabbit blood was dose dependent in goats and correlated well with changes in systemic arterial thromboxane B2 concentrations [change in pulmonary arterial pressure = 0.07 (thromboxane B2) + 8.3, r = 0.79]. We also tested the prostaglandin H2 endoperoxide analogue (U-46619) and found that the goats are somewhat more reactive than rabbits. We conclude that the pulmonary hemodynamic reaction to foreign blood is consistent with the concept that the foreign erythrocytes are reacting with the pulmonary intravascular macrophages in goats. The lower reactivity of the rabbit pulmonary circulation to thromboxane may also have a role.

Animals↗
PubMed1991

On writing abstracts.

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Abstracting and Indexing↗
PubMed1990

Caudal mediastinal node lymph flow in sheep after histamine or endotoxin infusions.

To determine whether intrathoracic nonpulmonary structures (caudal mediastinal node or esophagus) are reputed to affect lung lymph dynamics, we studied anesthetized, open-thorax, prone, ventilated sheep in which all lung afferent lymphatics to the caudal mediastinal node were eliminated. When we increased left atrial pressure by 20 cmH2O in four sheep, there was no effect on caudal mediastinal node efferent lymph flow or protein concentration, thus providing the completeness of the surgical preparation. In four sheep, intravenous histamine infusions (3 micrograms base.kg-1.min-1) had no effect on caudal mediastinal node lymph flow or protein concentration. In seven sheep with intact lung lymphatics, Escherichia coli endotoxin infusion (1 microgram/kg over 20 min) increased lymph flow with high lymph protein concentration during the late phase (2-6 h). In seven sheep, after all lung lymphatic afferents had been cut, endotoxin did not affect caudal mediastinal node lymph flow, although lymph protein concentration was decreased in the early 0-2 h, "hypertensive") phase. We conclude that at the concentrations tested, which are those regularly used in sheep lung experiments, the effects of histamine and endotoxin on caudal mediastinal node lymph flow and protein concentration are limited to the lung.

Animals↗
PubMed1990

Micropuncture pressure in small arteries or veins of perfused rabbit lungs.

Until now, direct micropuncture measurements of vascular pressure in lung have been limited to small vessels less than 100 microns on the pleural surface. On the other hand, direct pressure measurements using small catheters (less than 1-mm OD) in pulmonary vessels have been limited to those greater than 1.2 mm. We measured pressure in intermediate-sized microvessels (300-700 microns) using the micropuncture method in isolated perfused rabbit lungs. These microvessels are located 2 or 3 mm beneath the pleura. We exposed them by microsurgery and punctured the relatively thick-walled vessels with specially configured micropipettes. We exposed one pulmonary microvessel in each rabbit lung by microsurgery on the left middle lobe. In 15 rabbit lungs we measured pressure in a total of six small arteries (275- to 470-microns diam) and nine small veins (300- to 700-microns diam) under high zone 3 conditions, near the zone 2/3 boundary. We found approximately 35% of the total pulmonary vascular pressure drop in arteries greater than 275-microns diam and 7% in veins greater than 300-microns diam. In veins greater than 500-microns diam, there was no measurable pressure drop. After the measurements, we froze the lung and confirmed that there was no detectable interstitial or alveolar edema in the cross sections of the punctured site. Our data are compatible with those of other investigators who have used isolated perfused rabbit lungs under similar experimental conditions.

Animals↗
PubMed1990

Clearance of lung edema into the pleural space of volume-loaded anesthetized sheep.

To determine whether lung edema leaks into the pleural space, we measured flow rates of visceral pleural liquid from exposed sheep lungs during volume loading and then compared the protein concentration of visceral pleural liquid and lung interstitial liquids (lymph and peribronchovascular cuff liquid). For 4 h, we volume loaded 24 anesthetized ventilated sheep with one side, both sides, or neither side of the chest open. During the experiment, we collected visceral pleural liquid from a bag surrounding the exposed lung and lung lymph; after the experiment, we collected peribronchovascular cuff liquid. We found that during volume loading visceral pleural liquid flow increased significantly by 2 h, and its protein concentration over the final hour was the same as that of lung interstitial liquids. The volume of visceral pleural liquid correlated with excess lung water and wedge pressure elevation. By our estimates, clearance of edema from the lung into the pleural space constituted 23-29% of all edema liquid collected, similar to measured lymph edema clearance. We conclude that edema liquid leaks directly from edematous sheep lungs into the pleural space and that this leakage provides an important additional route of edema clearance.

Anesthesia↗
PubMed1990

Effects of dextran 70 on hemodynamics and lung liquid and protein exchange in awake sheep.

We studied the effect of intravenous dextran 70 infusion on lung liquid and protein exchange to determine whether its effects were due to altered hemodynamics or to altered microvascular permeability. In each of six instrumented awake sheep with chronic lung lymph fistulas, we performed three experiments: 1) control, 2) a 30-minute infusion of 1 l of 6% dextran 70, and 3) an infusion of 1 l of 0.9% NaCl. In addition to pulmonary hemodynamics and lymph dynamics, we measured the plasma-to-lung lymph equilibration rate of [125I] albumin. We followed all the sheep for 10 hours, including a 2-hour baseline period. Dextran was more effective in expanding plasma volume (63 +/- 15% [mean +/- SD]) than saline (11 +/- 6%) at the end of the 30-minute infusion. Pulmonary vascular pressures increased after dextran and remained elevated for 8 hours, whereas after saline the pressures returned to baseline within 1 hour. After dextran, lung lymph flow increased and remained elevated. It was only transiently increased after saline. We confirmed that dextran equilibrated rapidly with lung lymph (half-time, less than 0.6 hour), even though it maintained plasma volume expansion for the whole body (half-time, 11.1 +/- 2.7 hours). The dextran increased both plasma and lymph total macromolecular osmotic pressure but did not increase the plasma-interstitial (lymph) osmotic pressure difference in the lung, except transiently during the infusion. The lymph/plasma protein concentration ratio increased after dextran due mainly to plasma protein dilution. There were no differences in the half-time of tracer albumin equilibration between plasma and lung lymph (control, 2.2 +/- 0.6 hours; saline, 2.0 +/- 0.6 hours; dextran, 2.3 +/- 0.6 hours). Dextran 70 increased liquid filtration mainly by increasing microvascular pressure and possibly filtration surface area. There was no evidence for a change in the leakiness of the lung microvascular barrier to albumin.

Animals↗
PubMed1990

Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep.

In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury.

Acute Disease↗
PubMed1990

A new method for estimating filtration variables in isolated zone 1 rat lung.

The filtration variables, K (filtration coefficient), Ppmv (perimicrovascular pressure) and sigma (reflection coefficient), were estimated independently in previous reports using the Starling equation or the micropuncture method. We used matrix algebra to estimate these variables simultaneously. We measured filtration rate (Q) by a gravimetric method in isolated rat lung lobes in zone 1 conditions (alveolar pressure = 20 cmH2O) at two vascular pressures, Pvasc = 15 or 18 cm H2O and perfused the lobes with plasma containing a low or a high concentration of protein. By extrapolating the log of the rate of weight gain to t = 0, we obtain the initial filtration rate before any of the pressure variables (microvascular and perimicrovascular hydrostatic pressures) in the Starling equation changed. Assuming that protein filtered into perimicrovascular space only by convection, we substituted it into the Starling equation as follows: Q = K [(Pmv -- Ppmv) -- sigma 2 (IImv)], where Pmv and IImv are microvascular and perimicrovascular plasma protein osmotic pressures. IImv was estimated by Yamada's equation (Yamada et al. 1985). For the matrix algebra, we used three values, we omitted the value for the high protein, low vascular pressure experiment. We obtained K = 26.3 [mg/(min x cmH2O x g wet weight)], Ppmv = 6.2 cmH2O and sigma = 0.46. These values agree with values from previous reports. Since these 3 filtration variables are interrelated, this new method for simultaneous measurement is more accurate than independent measurements are. The chief advantage of this method is that it does not require a separate estimate of isogravimetric pressure or a direct measurement of interstitial pressure, and all variables are obtained simultaneously.

Algorithms↗
PubMed1989

Erythrocytes reduce liquid filtration in injured dog lungs.

In isolated, dog lung lobes with pulmonary vessels filled with different liquids, we measured the rate of weight gain for 5 or 10 min at constant alveolar and vascular pressures under zone 1 conditions (alveolar pressure greater than vascular pressure). We used six different liquids: syngeneic plasma, whole blood (hematocrit = 38 +/- 4%), 4% albumin in Krebs-Ringer solution, washed red blood cells in Krebs-Ringer solution (hematocrit = 37 +/- 6%), and platelet-rich or platelet-poor plasma. We studied the lobes under three conditions: immediate perfusion after removal (less than 30 min), delayed perfusion (2 h or more), or immediate perfusion after removal from air-embolized animals. In lobes that showed low-filtration rate using plasma [less than 0.5 g/(min x 100 g)] substitution of whole blood had no effect on the filtration rate. In lobes that showed high-filtration rates using plasma (delayed perfusion or deliberately injured using air emboli) substitution of whole blood caused a dramatic decrease in the filtration rate, restoring it to the level obtained in uninjured lobes. Platelets had no effect. Thus the red cells specifically reduced abnormally high filtration but did not affect normal filtration. There appear to be three possible mechanisms: 1) red cells physically blocking large leaks; 2) red cells settling on the filtration surface area (osmotic-barrier effect); 3) red cells acting as reducing agents against active oxygen metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Early detection of pulmonary congestion and edema in dogs by using lung sounds.

Five mongrel dogs (2 interstitial and 3 alveolar edema) were studied. Lung mechanics were measured by recording the flow, volume, and esophageal pressure according to the standard technique. Edema was produced by infusion of Ringer lactate solution. Lung sounds were recorded on tape from the dependent part of the chest wall. Lung sound signals were high-pass filtered at 100 Hz and subjected to fast Fourier transform. Samples of lung sounds were analyzed before (control) and at 5, 10, 20, 30, and 40 min after the infusion. The mean, median, and mode frequencies of sound power spectra at the control time were, respectively, 169.6 +/- 29.19, 129.6 +/- 29.81, and 136.0 +/- 29.87 (SD) Hz. These values increased significantly at 5 min after infusion to 194.0 +/- 26.08 (P less than 0.0037), 150.2 +/- 23.48 (P less than 0.0085), and 164.6 +/- 28.74 Hz (P less than 0.02), respectively. These values stayed significantly elevated at 10, 20, 30, and 40 min. The pulmonary wedge pressure, lung dynamic compliance, and pulmonary resistance were measured also at the same times. The mean, median, and mode frequencies correlated with pulmonary wedge pressure (P less than 0.00001, P less than 0.0001, P less than 0.0001), lung dynamic compliance (P less than 0.001, P less than 0.0001, P less than 0.0001), and pulmonary resistance (P less than 0.00001, P less than 0.00001, P less than 0.0001), respectively. There were no significant adventitious sounds up to 40 and 50 min after infusion. We concluded that pulmonary congestion and early edema alter the frequency characteristics of lung sounds early, before the occurrence of adventitious sounds. These altered lung sounds may be used as an index of pulmonary congestion and impending edema.

Animals↗
PubMed1989

[Estimation of the filtration variables in the rat lung].

The filtration variables, filtration coefficient (K), perimicrovascular pressure (Ppmv) and reflection coefficient (sigma) were estimated independently in previous reports using the Starling Equation or the micropuncture method. We estimated these variables simultaneously. We measured filtration rate by a gravimetric method in isolated rat lung lobes in zone 1 conditions (alveolar pressure = 20 cmH2O) at two vascular pressures, Pvasc = 15 or 8 cmH2O and perfused the lobes with plasma containing a low or high concentration of protein. By extrapolating the log of the rate of weight gain to time = 0, we obtain the initial filtration rate. Assuming that protein filtered into perimicrovascular space only by convection, we substituted into the Starling Equation as follows: Q = K[(Pmv-Ppmv)-sigma 2 pi mv], where Pmv and pi mv are hydrostatic and plasma protein osmotic pressures in microvascular space. pi mv was estimated by Yamada's equation. We obtained K = 26.3 +/- 8.7 mg/(min.cmH2O.g), PPMV = 6.2 +/- 0.7 cmH2O, sigma = 0.46 +/- 0.07. The chief advantages of this method are that it does not require a separate estimation of isogravimetric pressure or a direct measurement of interstitial pressure, and that all variables are obtained simultaneously.

Animals↗
PubMed1988

New concepts about the pathophysiology of pulmonary edema.

Three new concepts concerning lung liquid and protein exchange are considered. The first is that the microvascular surface area is as important as the microvascular hydrostatic pressure in assessing filtration in the lung. One of the problems in differentiating hemodynamic from increased permeability edema is the inability to determine whether the microvascular surface area has changed. Several agents, as well as exercise, affect liquid filtration. A new, dynamic procedure that is more sensitive for the detection of increased permeability than static measurements of lung water content is described, along with its limitations. The second concept is that water and electrolytes are cleared from the alveoli by a separate mechanism from protein. Water clearance is fast and occurs mainly by an active process, which can be inhibited by amiloride or phloridzin and accelerated by beta-agonists. The mechanism appears to depend on metabolically regulated sodium transport across the alveolar epithelium. Protein clearance is very slow and is relatively independent of alveolar concentration. The protein clearance mechanism is unknown but may involve transcytosis. The third concept is that during edema formation there are two pathways for liquid clearance in addition to the lymphatic system: into the pleural space and along the bronchovascular connective tissue into the mediastinum. During recovery from edema, reabsorption into blood is important if the edema liquid has a low protein osmotic pressure. Clearance into the mediastinum may be the major pathway for liquid sequestered in the loose, binding connective tissue.

Animals↗
PubMed1988

Removal of pleural liquid and protein by lymphatics in awake sheep.

The contribution of the parietal pleural lymphatics to pleural liquid and protein removal is unclear. We asked two questions. What is the rate of removal of sterile, artificial hydrothoraxes in awake sheep? What percentage is removed through parietal pleural lymphatics? Three days after the placement of a rib capsule in 18 sheep, we instilled a 10 ml/kg 1.0 g/dl autologous protein solution with labeled albumin and erythrocytes through the capsule into the pleural space. Erythrocytes were used as a marker for lymphatic flow. We measured terminal pleural liquid volume and radioactivity at periods from 2 to 48 h. In three sheep, we obtained a third volume measurement at 6 h by the volume of dilution technique. We found that hydrothorax removal could be described by a linear function with a constant rate: 0.28 +/- 0.01 ml.kg-1.h-1 (mean +/- SE) for the grouped data, and 0.20, 0.28, and 0.31 ml.kg-1.h-1 for the individual sheep. At 24 h, erythrocyte clearance was 89 +/- 16% (mean +/- SD) that of liquid and albumin clearance. We conclude that in awake sheep with large hydrothoraxes, pleural liquid and protein are removed at a rate of 0.28 +/- 0.01 ml.kg-1.h-1 (mean +/- SE) and lymphatics are responsible for at least 89% of this removal.

Animals↗
PubMed1988

Continuous measurement of protein osmotic pressure in blood and lymph of sheep.

We have continuously measured protein osmotic pressure of blood and lymph in sheep to compare two kinds of needle osmometers (rigid and flexible) with a membrane osmometer (Wescor). We also compared the averaged values of the continuous measurement with osmotic pressure calculated from total protein and albumin fraction, using the Yamada equation. The rigid-needle and membrane osmometers showed excellent correlation (y = 1.00x + 0.06; r greater than 0.99). The flexible-needle osmometer tended to overestimate osmotic pressure (avg 16%). We used the rigid-needle osmometer for continuous measurements of protein osmotic pressure of blood and lymph in anesthetized or unanesthetized sheep to observe changes in protein osmotic pressure of blood and lymph through the three different interventions. The relationship between the theoretical values (x) and the continuous measurements (y) of osmotic pressure was good (y = 0.99x + 0.16, r = 0.97), but after various interventions, the continuously measured protein osmotic pressure tended to exceed the calculated measurements. The continuous measurement should be monitored with spot samples measured in a stationary osmometer or by calculation of osmotic pressure from total protein concentration and albumin fraction.

Animals↗