Endothelial extraction of tracer water is independent of temperature in dog lungs

1986 ◽  
Vol 250 (6) ◽  
pp. H1017-H1021
Author(s):  
F. P. Chinard ◽  
W. O. Cua

Diffusion and viscosity-dependent flow rates generally decrease with decrease of temperature in biological systems. We have examined the extraction (Ec) of tracer water in isolated dog lungs perfused near 37 degrees C and near 15 degrees C with multiple-indicator dilution experiments. If Ec were barrier limited, Ec should be less at lower temperatures. Two runs at 37 degrees C were followed by two runs at 15 degrees C. Evans blue (T-1824) was used as vascular reference, and tritium oxide (THO) was used as water tracer. Values of Ec were based on the ratio of the areas under the two indicator curves from appearance time to time of peak of T-1824. Values for permeability-surface area (PS) products were calculated from the classical Crone relationship in 14 experiments with a total of 56 runs. Neither Ec nor PS decreased with temperature. Instead, modest but statistically significant increases were found. We conclude that the extraction of tracer water in these preparations is not barrier limited.

1985 ◽  
Vol 249 (1) ◽  
pp. H141-H149 ◽  
Author(s):  
J. B. Bassingthwaighte ◽  
J. T. Kuikka ◽  
I. S. Chan ◽  
T. Arts ◽  
R. S. Reneman

Multiple indicator-dilution experiments were done to compare the transcapillary exchange of tracer amounts of L-[14C]ascorbate and D-[3H]glucose (against an intravascular reference 131I-albumin) in Ringer-perfused (5 mM glucose) isolated rabbit hearts. The indicator-dilution curves for the two were virtually superimposed over the first 40-80 s. Estimates of the capillary permeability-surface area products, PSc, were the same, 2.3 +/- 0.7 (SD) ml X g-1 X min-1 (n = 18), in accord with the coincidence of their instantaneous extractions. The similarity of glucose and ascorbate permeabilities is explained by the similarity in molecular weights and passive diffusivity, their lipophobic nature, and the paucity of carrier-mediated endothelial transport for either molecule. The data were analyzed via a model composed of aggregates of spatially distributed capillary-tissue units (capillary blood, interstitium, myocytes) accounting for the heterogeneity of regional flows. The interstitial volumes in this preparation are enlarged, 0.30 +/- 0.04 ml/g. There is substantial entry into myocardial cells, the cell permeability-surface area products being approximately 2-3 ml X g-1 X min-1 for ascorbate and glucose. The estimated volumes of interstitial and intracellular space, 0.30 and 0.47 ml X g-1 X min-1, reflect interstitial edema and are very close to measured values, giving reassurance concerning the methods of modeling analysis.


1997 ◽  
Vol 83 (6) ◽  
pp. 1976-1985 ◽  
Author(s):  
Joseph W. Klaesner ◽  
N. Adrienne Pou ◽  
Richard E. Parker ◽  
Charlene Finney ◽  
Robert J. Roselli

Klaesner, Joseph W., N. Adrienne Pou, Richard E. Parker, Charlene Finney, and Robert J. Roselli. Optical measurement of isolated canine lung filtration coefficients at normal hematocrits. J. Appl. Physiol. 83(6): 1976–1985, 1997.—In this study, lung filtration coefficient ( K fc) values were measured in eight isolated canine lung preparations at normal hematocrit values using three methods: gravimetric, blood-corrected gravimetric, and optical. The lungs were kept in zone 3 conditions and subjected to an average venous pressure increase of 10.24 ± 0.27 (SE) cmH2O. The resulting K fc(ml ⋅ min−1 ⋅ cmH2O−1 ⋅ 100 g dry lung wt−1) measured with the gravimetric technique was 0.420 ± 0.017, which was statistically different from the K fc measured by the blood-corrected gravimetric method (0.273 ± 0.018) or the product of the reflection coefficient (ςf) and K fc measured optically (0.272 ± 0.018). The optical method involved the use of a Cellco filter cartridge to separate red blood cells from plasma, which allowed measurement of the concentration of the tracer in plasma at normal hematocrits (34 ± 1.5). The permeability-surface area product was measured using radioactive multiple indicator-dilution methods before, during, and after venous pressure elevations. Results showed that the surface area of the lung did not change significantly during the measurement of K fc. These studies suggest that ςf K fccan be measured optically at normal hematocrits, that this measurement is not influenced by blood volume changes that occur during the measurement, and that the optical ςf K fcagrees with the K fc obtained via the blood-corrected gravimetric method.


2000 ◽  
Vol 279 (4) ◽  
pp. H1502-H1511 ◽  
Author(s):  
Lisa M. Schwartz ◽  
Thomas R. Bukowski ◽  
James D. Ploger ◽  
James B. Bassingthwaighte

Adenosine (Ado), a smooth muscle vasodilator and modulator of cardiac function, is taken up by many cell types via a saturable transporter, blockable by dipyridamole. To quantitate the influences of endothelial cells in governing the blood-tissue exchange of Ado and its concentration in the interstitial fluid, one must define the permeability-surface area products ( PS) for Ado via passive transport through interendothelial gaps [ PS g(Ado)] and across the endothelial cell luminal membrane ( PS ecl) in their normal in vivo setting. With the use of the multiple-indicator dilution (MID) technique in Krebs-Ringer perfused, isolated guinea pig hearts (preserving endothelial myocyte geometry) and by separating Ado metabolites by HPLC, we found permeability-surface area products for an extracellular solute, sucrose, via passive transport through interendothelial gaps [ PS g(Suc)] to be 1.9 ± 0.6 ml · g−1 · min−1( n = 16 MID curves in 4 hearts) and took PS g(Ado) to be 1.2 times PS g(Suc). MID curves were obtained with background nontracer Ado concentrations up to 800 μm, partially saturating the transporter and reducing its effective PS ecl for Ado. The estimated maximum value for PS ecl in the absence of background adenosine was 1.1 ± 0.1 ml · g−1 · min−1 [maximum rate of transporter conformational change to move the substrate from one side of the membrane to the other (maximal velocity; V max) times surface area of 125 ± 11 nmol · g−1 · min−1], and the Michaelis-Menten constant ( K m) was 114 ± 12 μM, where ± indicates 95% confidence limits. Physiologically, only high Ado release with hypoxia or ischemia will partially saturate the transporter.


1995 ◽  
Vol 269 (5) ◽  
pp. H1811-H1819
Author(s):  
W. O. Cua ◽  
V. Bower ◽  
C. Tice ◽  
F. P. Chinard

Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO) were assessed in dog lungs by multiple indicator-dilution experiments in vivo with anesthesia and in isolated perfused preparations before and after alveolar flooding. In controls, outflow patterns of AP and THO were nearly identical. In flooding, AP and THO patterns separated. THO upslopes decreased and mean (t) and modal (tmax) transit times increased as flooding increased; AP initial upslopes remained relatively unchanged but t increased, whereas tmax decreased. Patterns of 22Na+ were unchanged. The results indicate 22Na+ limitation at the endothelium, AP limitation only at the epithelium, and no THO limitation. A mathematical model is based on axial and orthogonal distribution of AP and THO. With alveolar flooding, diffusional distance may be a limiting factor in this distribution.


1992 ◽  
Vol 72 (2) ◽  
pp. 505-514 ◽  
Author(s):  
V. J. Abernathy ◽  
R. J. Roselli ◽  
R. E. Parker ◽  
N. A. Pou

We studied the effects of three different doses (15, 20, and 25 mg/kg) of Perilla ketone (PK) on the blood-perfused in situ sheep lung while obtaining external measurements of lung transvascular protein flux. Lymph flow and lymphatic protein clearance increased significantly after all doses of PK. Severe pulmonary edema was confirmed by high postmortem wet-to-dry lung weight ratios and increased extravascular lung water from multiple indicator-dilution studies. Urea permeability-surface area product and effective diffusivity from multiple indicator-dilution studies also increased after PK infusion. Because we observed no evidence of increased capillary pressure or increased microvascular surface area after PK, we conclude that PK significantly increased pulmonary microvascular permeability. Certain aspects of the in situ PK response appeared to be dose dependent. The lungs responded rather quickly to high doses of PK, but an apparent latency period was noted with low doses of PK. Postmortem wet-to-dry lung weight ratios were always high but did not suggest dose dependence. However, times of postmortem measurements were not the same for all doses of PK. The external scan technique appeared to be sensitive to changes that occurred in the lung after PK. Externally detected albumin interstitial-to-plasma mass (mass I/P) ratios were substantially higher after PK than during control in situ studies. In some experiments, final mass I/P ratios increased above 4 approximately 2.0 h after PK compared with control values of 0.2 and 0.4. A delay time between injection and change in mass I/P slope was also observed, which decreased with increasing dose of PK. PK causes a permeability injury in the in situ sheep lung and provides a useful model for studying the sensitivity of permeability measurement techniques such as the external gamma-ray detection method.


1986 ◽  
Vol 61 (4) ◽  
pp. 1383-1387 ◽  
Author(s):  
R. E. Parker ◽  
R. J. Roselli ◽  
F. R. Haselton ◽  
T. R. Harris

Seven dog lower left lung lobes were statically inflated and perfused at a constant rate for each lobe with a perfusate in which the hematocrit was altered over a wide range. The permeability-surface area of urea was calculated from multiple indicator dilution curves using two separate injectates for each hematocrit level. One injectate contained only 125I-albumin as the vascular reference tracer and the other contained both 51Cr-erythrocytes and 125I-albumin as the vascular reference tracers; both contained [14C]urea as the permeating tracer. The results strongly indicate that the phenomenon of “erythrocyte trapping” of urea does not affect the calculation of urea permeability-surface area product provided the appropriate albumin-erythrocyte composite reference tracer is utilized in its calculation.


2000 ◽  
Vol 278 (5) ◽  
pp. G775-G788 ◽  
Author(s):  
Carl A. Goresky ◽  
Glen G. Bach ◽  
André Simard ◽  
Andreas J. Schwab ◽  
Adelar Bracht

Multiple-indicator dilution experiments with labeled lactate were performed in the livers of anesthetized dogs. A mixture of51Cr-labeled erythrocytes, [3H]sucrose, andl-[1-14C]lactate or a mixture of51Cr-labeled erythrocytes, [14C]sucrose, andl-[2-3H]lactate was injected into the portal vein, and samples were obtained from the hepatic vein. Data were evaluated using a model comprising flow along sinusoids, exchange of lactate between plasma and erythrocytes and between plasma and hepatocytes, and, in the case ofl-[1-14C]lactate, metabolism to H[14C][Formula: see text]within hepatocytes. The coefficient for lactate efflux from erythrocytes was 0.62 ± 0.24 s−1, and those for influx into and efflux from hepatocytes were 0.44 ± 0.13 and 0.14 ± 0.07 s−1, respectively. The influx permeability-surface area product of the hepatocyte membrane for lactate ( P in S, in ml ⋅ s−1 ⋅ g−1) varied with total flow rate ( F, in ml s−1 ⋅ g−1) according to P in S = (3.1 ± 0.5) F+ (0.021 ± 0.014). Lactate in plasma, erythrocytes, and hepatocytes was close to equilibrium, whereas lactate metabolism was rate limiting.


2003 ◽  
Vol 95 (1) ◽  
pp. 279-291 ◽  
Author(s):  
Andreas J. Schwab ◽  
Agnés Salamand ◽  
Yahye Merhi ◽  
André Simard ◽  
Jocelyn Dupuis

Multiple-indicator-dilution experiments were performed in the lungs of 13 anesthetized dogs by simultaneous bolus injection of 111In-labeled neutrophils, 51Cr-labeled red blood cells, and Evans blue-labeled albumin. Concomitant counts of unlabeled neutrophils were similar in pulmonary artery and aortic blood samples, demonstrating a dynamic balance across the lungs in the physiological state. Outflow profiles of labeled neutrophils were analyzed on the basis of a recirculatory pharmacokinetic model of labeled albumin. The outflow profiles of the recovered neutrophils were composed of a throughput component of circulating neutrophils and a component of reversibly marginated neutrophils. They were interpreted by a model incorporating neutrophil margination (transfer coefficient = 0.195 ± 0.081 s-1), rapid demargination (0.054 ± 0.027 s-1), and transfer to a slow marginated pool (0.023 ± 0.018 s-1). It will be interesting to apply the analysis in future studies aimed at determining whether it could be a useful research tool to investigate the interactions between the pulmonary endothelium and neutrophils in physiological and diseased states.


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