Metabolism of [2-14C]Prostaglandin E1 on Passage Through the Pulmonary Circulation

1975 ◽  
Vol 53 (4) ◽  
pp. 610-615 ◽  
Author(s):  
Christopher A. Dawson ◽  
Bruce O. Cozzini ◽  
Andrew J. Lonigro

A multiple indicator dilution technique was used to study inactivation of [14C] prostaglandin E1 (PGE1) by isolated cat lungs. A bolus containing [2-14C]PGE1, indocyanine green dye and 3HOH was rapidly introduced into the blood entering the pulmonary artery. Sequential samples of the venous effluent were collected and analyzed for 3H, dye, and 14C. The 14C-labelled compounds were separated by thin-layer chromatography, and the quantity of PGE, and its metabolites contained in each sample was determined (radiochromatogram scanning). Recovery of the dye and 3H was complete within the sampling period. However, only 79% of the injected 14C emerged from the lung within this period, 36% as [14C]PGE1, and 43% as two less polar metabolites. The mean transit times (including connecting tubing) for the unmetabolized [14C]PGE1 and the dye were 9.1 and 8.7 s, respectively. The apparent mean transit times for 14C in the metabolites were considerably longer, 12.4 and 14.3 s. The 3HOH mean transit time was 10.7 s. These data are compatible with an extraluminal site for PGE1 metabolism.

1992 ◽  
Vol 73 (2) ◽  
pp. 557-562 ◽  
Author(s):  
S. Rimar ◽  
C. N. Gillis

Substantial removal of the vasoconstrictor peptide endothelin-1 (ET-1) by the pulmonary circulation has been reported to occur in perfused guinea pig and rat lungs. We examined the uptake of ET-1 by coronary and pulmonary circulations of the rabbit by measuring single-pass extraction of ET-1 in the isolated heart and lung. In separate experiments, each organ was perfused at 30 ml/min with Krebs-albumin (3%) solution. A bolus of 125I-ET-1 and [14C]dextran in 0.3 ml Krebs-albumin solution was injected, and extraction of endothelin (EET), relative to that of an intravascular reference indicator, [14C]dextran, was determined by multiple indicator-dilution technique. EET was 5 +/- 2% (SE) in the heart and 49 +/- 4% in the lung. Increasing flow rate in the lung preparation to approximate the mean transit time in the heart preparation did not significantly alter EET. Despite insignificant uptake of ET-1, the coronary circulation extracted an angiotensin-converting enzyme inhibitor (351A) and metabolized a synthetic angiotensin-converting enzyme substrate (benzoyl-phenyl-alanyl-proline), both properties of the normal pulmonary circulation. We therefore conclude that there is no significant ET-1 uptake in the coronary vascular bed.


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.


1988 ◽  
Vol 255 (2) ◽  
pp. H375-H385 ◽  
Author(s):  
M. Miniati ◽  
J. C. Parker ◽  
M. Pistolesi ◽  
J. T. Cartledge ◽  
D. J. Martin ◽  
...  

The reabsorption of albumin from the pleural space was measured in eight dogs receiving 0.5 ml intrapleural injection of 131I-labeled albumin and a simultaneous intravenous injection of 125I-labeled albumin. Plasma curves for both tracers were obtained over 24 h. The 125I-albumin curve served as input function of albumin for interstitial spaces, including pleura, whereas the 131I-albumin curve represented the output function from pleural space. The frequency function of albumin transit times from pleural space to plasma was obtained by deconvolution of input-output plasma curves. Plasma recovery of 131I-albumin was complete by 24 h, and the mean transit time from pleura to plasma averaged 7.95 +/- 1.57 (SD) h. Albumin reabsorption occurred mainly via lymphatics as indicated by experiments in 16 additional dogs in which their right lymph ducts or thoracic ducts were ligated before intrapleural injection. A pleural lymph flow of 0.020 +/- 0.003 (SD) ml.kg-1.h-1 was estimated, which is balanced by a comparable filtration of fluid into the pleural space. This suggests that, under physiological conditions, the subpleural lymphatics represent an important control mechanism of pleural liquid pressure.


1984 ◽  
Vol 56 (4) ◽  
pp. 878-890 ◽  
Author(s):  
B. A. Gray ◽  
R. C. Beckett ◽  
R. C. Allison ◽  
D. R. McCaffree ◽  
R. M. Smith ◽  
...  

The extravascular thermal volume of the lung (ETV) has been measured in dogs as the difference between mean transit time (t) volumes for heat and indocyanine green dye across the pulmonary circulation, calculated as the product of thermal dilution cardiac output (CO) and the difference in t for aortic indicator-dilution curves generated by right and left atrial injections. ETV measurements were compared with the extravascular lung mass (ELM): in 21 normal dogs, ETV/ELM = 1.11 +/- 0.14 (SD); in 17 dogs with hydrostatic pulmonary edema (up to 21 g/kg), ETV/ELM = 0.90 +/- 0.11; and in 27 dogs with alloxan pulmonary edema (up to 51 g/kg); ETV/ELM = 0.93 +/- 0.13. For all 65 dogs the mean ETVELM was 0.98 +/- 0.15, and the liner regression was ETV (ml/kg) = 0.90 ELM (g/kg) + 0.86 +/- 2.25 (SEE; r = 0.96). Calculations based on measurements of lung specific heat predict that ETV/ELM should equal 0.984. With acute changes in pulmonary hemodynamics, ETV was reduced by reductions in pulmonary arterial pressure (Ppa) sufficient to produce zone 1 conditions at the top of the lung. However, ETV was not affected by increases in CO (mean = 50%) produced by nitroprusside or by increases in Ppa and pulmonary blood volume (mean = 27%) produced by partial mitral valve obstruction. Distortion of the thermal dilution curve due to position of the arterial thermistor appears to be the greatest source of variability and overestimation. Simultaneous measurements from pairs of thermistors differed by 14% (range 0.4–50%).


1983 ◽  
Vol 245 (4) ◽  
pp. F485-F495
Author(s):  
C. Whiteside ◽  
M. Silverman

The multiple-indicator-dilution (MID) technique was used to separate solute flux (Js) across the glomerular and postglomerular capillaries in vivo. Anesthetized mongrel dogs (n = 20) during mannitol diuresis received a pulse of extracellular indicators including 125I-albumin (plasma reference), [14C]inulin (glomerular reference), creatinine (interstitial reference), and a neutral [3H]dextran (specific mol wt between 10,000 and 24,000 dalton) in the left renal artery. Left renal venous and ureteric outflows were rapidly sampled. 3H-labeled dextrans 10,000-15,500 had renal vein mean transit times (t) greater than those of 125I-albumin, indicating postglomerular extraction. 3H-labeled dextrans greater than 15,500 had t values identical to those of 125I-albumin, indicating only unidirectional glomerular extraction. The glomerular fractional dextran extractions relative to simultaneously injected [14C]inulin (ED/Ei) were calculated from urine and renal vein outflow curves and ranged from 0.98 +/- 0.02 to 0.33 +/- 0.12 (SD) for mol wt 10,000 +/- 24,000. ED/Ei values were quantitatively identical to constant-infusion fractional clearances of the same dextrans. Renal plasma flow (RPF) was then deliberately reduced two-to threefold in the same dog. ED/Ei as measured by the MID technique remained unchanged during graded reduction in RPF. In constant-infusion experiments RPF was reduced from 5.78 to 2.77 ml X s-1 X 100 g-1 and GFR from 50.4 to 36.3 ml X min-1, but the fractional neutral dextran clearances remained constant. The predominance of convective solute flux across the dog glomerulus permitted calculation of glomerular reflection coefficients 0.03 +/- 0.06 to 0.85 +/- 0.03 (SD) for neutral 3H-labeled dextrans 10,000-24,000 dalton.


2018 ◽  
Vol 18 (10) ◽  
pp. 7439-7452 ◽  
Author(s):  
Xiaokang Wu ◽  
Huang Yang ◽  
Darryn W. Waugh ◽  
Clara Orbe ◽  
Simone Tilmes ◽  
...  

Abstract. The seasonal and interannual variability of transport times from the northern midlatitude surface into the Southern Hemisphere is examined using simulations of three idealized “age” tracers: an ideal age tracer that yields the mean transit time from northern midlatitudes and two tracers with uniform 50- and 5-day decay. For all tracers the largest seasonal and interannual variability occurs near the surface within the tropics and is generally closely coupled to movement of the Intertropical Convergence Zone (ITCZ). There are, however, notable differences in variability between the different tracers. The largest seasonal and interannual variability in the mean age is generally confined to latitudes spanning the ITCZ, with very weak variability in the southern extratropics. In contrast, for tracers subject to spatially uniform exponential loss the peak variability tends to be south of the ITCZ, and there is a smaller contrast between tropical and extratropical variability. These differences in variability occur because the distribution of transit times from northern midlatitudes is very broad and tracers with more rapid loss are more sensitive to changes in fast transit times than the mean age tracer. These simulations suggest that the seasonal–interannual variability in the southern extratropics of trace gases with predominantly NH midlatitude sources may differ depending on the gases' chemical lifetimes.


1981 ◽  
Vol 61 (6) ◽  
pp. 765-771 ◽  
Author(s):  
Maria Monica Elias ◽  
E. J. Comin ◽  
Susana Galeazzi ◽  
E. A. Rodriguez Garay

1. the interaction of unconjugated bilirubin with peritubular cell membranes of the rat kidney was studied by means of an isolated rat-kidney preparation applying the multiple-indicator-dilution technique. 2. Inulin was used as an extracellular marker and p-aminohippuric acid as a model of organic anion that interacts with the peritubular membrane. 3. A single renal artery injection of a mixture containing inulin and unconjugated bilirubin was followed by the appearance of the two compounds in the venous effluent. the unconjugated bilirubin curve was always under the curve of inulin and its mean transit time was always less than that for inulin. 4. the cumulative venous recovery of inulin was higher than that of unconjugated bilirubin. 5. When unconjugated bilirubin uptake was plotted against the injected dose of pigment the relationship suggested a saturation phenomenon. 6. the recovery of p-aminohippuric acid was significantly increased when unconjugated bilirubin was added. 7. the results provide evidence for the interaction of unconjugated bilirubin with the peritubular cell membranes of rat kidney.


1988 ◽  
Vol 27 (05) ◽  
pp. 188-194 ◽  
Author(s):  
V. Kempi

Seventy patients were studied with a dual radionuclide technique. The conventional renograms and the blood curve were subjected to deconvolution analysis using the matrix algorithm method, and the following curve data calculated from the retention functions: absolute and relative amplitudes, minimum time of the retention function, maximum time of the retention function and mean transit time. The findings with the two radiopharmaceuticals 99mTc-DTPA and 131l-Hippuran were compared under normal and pathological conditions. The correlations between the data with 99mTc-DTPA and those with 131l-Hippuran were highly significant (p <0.01). So was the correlation between the absolute amplitude of the retention curve and the rate of uptake based on the corresponding renogram (p <0.01). Due to the difference in the renal handling of the two tracers, longer maximum times were obtained with 99mTc-DTPA. The mean transit times were also longer with 99mTc-DTPA, except in kidneys with parenchymal insufficiency. The highest amplitudes were found in normal kidneys, while the lowest values were observed in parenchymal insufficiency. In the group with acute ureteral obstruction, the mean transit times tended to be increased. The maximum times were even more increased. With both tracers it is possible to distinguish between the three groups of renal conditions studied here: Normal, parenchymal insufficiency, and acute ureteral obstruction.


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.


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