Uptake of lactate by the liver: effect of red blood cell carriage

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.

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.


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.


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.


1995 ◽  
Vol 78 (4) ◽  
pp. 1350-1359 ◽  
Author(s):  
D. F. Cousineau ◽  
C. A. Goresky ◽  
C. P. Rose ◽  
A. Simard ◽  
A. J. Schwab

The roles of blood flow, local oxygen consumption, and perfusion pressure on cardiac transcapillary exchange were characterized in closed-chest anesthetized dogs by use of the multiple-indicator dilution technique. Occlusion of the carotid arteries or injection of dipyridamole increased coronary flow to significantly higher values compared with a group of animals in a basal state obtained in a previous study. Carotid occlusion resulted in a significant increase in perfusion pressure and myocardial oxygen consumption, whereas these two variables were significantly reduced after dipyridamole. For the whole group of animals, the capillary permeability-surface area product for sucrose increased with coronary flow, which appeared to be the important controller for this microcirculatory exchange parameter. Perfusion pressure and myocardial oxygen consumption also regulated permeability-surface area product values, although to a lesser extent than flow. The heterogeneity of transit times in the capillaries was reduced at high coronary flow values, despite large differences in the cardiac utilization of oxygen. The data suggest that cardiac capillary exchange responds mostly to hemodynamic changes originating at the precapillary level.


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.


1982 ◽  
Vol 242 (5) ◽  
pp. F436-F446
Author(s):  
C. Trainor ◽  
M. Silverman

The permselectivity of the postglomerular capillary wall was studied by performing pulse-injection multiple indicator-dilution experiments on dog kidneys in vivo, using simultaneous injection of T1824-labeled albumin (plasma reference), creatinine (extracellular reference), and one or two radioactively labeled indicators: raffinose (595 dalton), vitamin B12 (1,357 dalton), or inulin (approximately 5,000 dalton). The urine transit patterns superimposed for all these except albumin, suggesting equal permeability for these molecular weight markers at the level of the glomerular filtration barrier. But the renal vein mean transit times progressively decreased. Therefore, their apparent interstitial volumes of distribution decrease with increasing molecular weight. This could be due to several factors acting singly or in combination: reduced capillary permeability in the postglomerular microcirculation; restricted diffusion in the postglomerular interstitium; or excluded volume effects. Evidence suggested that the effect was due to a combination of permeability and exclusion volume effects. To assess the validity of this assumption, the barrier-limited model was compared with the experimental data. The results were analyzed (both hydropenic and mannitol-diuretic dogs) and best fits calculated using two independent parameters, permeability and excluded volume. For permeability (X10(-4) cm/s, mean +/- SD) the range of values was always greater than or equal to 15 for creatinine and raffinose, and greater than or equal to 12 for B12. The permeability for inulin was 6.9 +/- 1.4. When interstitial volume excluded was expressed as percentage of the volume available to creatine, the excluded volume was negligible for raffinose and B12 but 12 +/- 5% for inulin. During mannitol diuresis the permeability for creatinine and raffinose remained high, but the values tended to decrease for B12. The permeability of inulin decreased to 2.9 +/- 0.09. Mannitol diuresis increased the excluded volume of inulin but did not alter the creatinine, raffinose, or B12 value.


1987 ◽  
Vol 252 (2) ◽  
pp. H340-H348 ◽  
Author(s):  
F. P. Chinard ◽  
W. O. Cua

In multiple indicator-dilution experiments, transvascular passage of a permeating indicator is conventionally derived from the up-slope separation of the curve of the permeating indicator from that of a vascular reference and is expressed as the extraction (Ec). Extraction may be limited by the barrier (barrier-limited distribution). It may be limited by the volume of distribution accessible to it; in the time domain of an indicator-dilution experiment, the passage to and distribution in the extravascular volume are rapid relative to the velocity of blood in the exchange vessels. We examine here the relations of the extraction of tracer water as tritium oxide (THO) [Ec(THO)] and of the extraction of tracer sodium as 22Na [Ec(22Na)] to extravascular lung water, delta V wev, by adding isotonic fluid to the gas phase of the lungs. The net convective transvascular passage of water is negligible relative to the transendothelial molecular exchange. In 10 experiments in vivo and in 10 experiments in isolated perfused lungs, Ec(THO) increases as delta V wev increases. Ec(22Na) and the permeability-surface area product (PS) for 22Na do not change as delta V wev increases. We conclude that the extraction of THO is determined mainly by the volume accessible to it (flow- or volume-limited distribution) and that the extraction of 22Na is determined mainly by the resistance of the endothelium (barrier-limited distribution). A diffusion limitation in the added alveolar fluid rather than a barrier limitation at the endothelium may moderate Ec(THO).


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.


1984 ◽  
Vol 57 (5) ◽  
pp. 1412-1416 ◽  
Author(s):  
G. A. Laine ◽  
R. E. Drake ◽  
F. G. Zavisca ◽  
J. C. Gabel

Estimates of the pulmonary microvascular membrane reflection coefficient (sigma) and permeability-surface area product (PS) are frequently made with the assumption that a percent change in transmicrovascular fluid flux (Jv) will be represented by an equal percent change in the lymph flow rate (QL) from a single cannulated lung lymph vessel. To test this, we measured QL in seven anesthetized dogs with the outflow end of the lymph cannula set at several heights (H) above and below the lung hilus. The left atrial pressure was then elevated to increase Jv, and QL was again measured at several H's. The percent increase in QL at elevated left atrial pressure depended on H. We used the QL data and lymph and plasma protein concentrations to estimate sigma and PS with a modified form of the Kedem and Katchalsky equations. The calculated values varied considerably with H. Our results indicate that changes in Jv are not represented by equal changes in QL. Therefore, techniques for estimating permeability that depend upon QL as an estimate of Jv may lead to erroneous estimates of sigma and PS.


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