Comparative Kinetics of Microvascular Inulin and 99mTc-Labelled Diethylenetriaminepenta-Acetic Acid Exchange

1997 ◽  
Vol 93 (5) ◽  
pp. 471-477 ◽  
Author(s):  
C. Cousins ◽  
R. D. Gunasekera ◽  
M. Mubashar ◽  
S. Mohammadtaghi ◽  
R. Strong ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Plasma Clearance ◽  
Interstitial Space ◽  
Second Phase ◽  
Time Activity ◽  
Deconvolution Analysis ◽  
Clearance Curve ◽  
Extraction Fraction ◽  
Time Courses ◽  
Arterial Plasma

1. After simultaneous intravenous injection as a mixture, 99mTc-labelled diethylenetriaminepentaacetic acid (99mTc-DTPA; molecular mass 492 Da) and inulin (∼6000 Da) gave arterial plasma clearance curves consisting of three exponentials, the time courses of which were not significantly different between the two solutes. 2. The ratio of 99mTc-DTPA to inuiin concentration in antecubital venous plasma (normalized to the ratio in arterial plasma at 30 s) was 0.6, significantly less than unity, within 2 min after intravenous injection, but increased to reach unity by 60 min. The minimun concentration ratio of 99mTc-DTPA to inulin in arterial plasma was 0.75 at 4 min, also rising to just above unity at 60 min. 3. The extraction fraction from plasma to interstitial space was higher for 99mTc-DTPA (∼0.5) than for inuiin (∼0.2). For both solutes, the net extraction fraction decreased with time, becoming negative at about 25 min after injection. Thereafter, the net extraction fractions remained negative, between −0.05 and −0.1, and not significantly different between the two solutes. 4. 99mTc-DTPA time—activity curves recorded over the limbs with scintillation probes were biphasic, with an initial phase corresponding closely in time with the first exponential of the arterial 99mTc-DTPA plasma clearance curve. The second phase corresponded in time to the intermediate exponential of the arterial 99mTc-DTPA plasma clearance curve. 5. The time course of net 99mTcm-DTPA extraction fraction across the forearm vascular bed was bi-exponential, with phases corresponding in time with the two phases of the limb uptake curves. 6. Deconvolution analysis of the limb time—activity curves, using the arterial time—concentration curve as the input function, gave bi-exponential 99mTc-DTPA impulse response curves in which the time courses of the exponentials corresponded with the first and intermediate exponentials of the arterial 99mTc-DTPA clearance curve. 7. The bi-exponential nature of the equilibrium of 99mTc-DTPA between vascular and interstitial compartments suggests the presence of two separate functional volumes within the interstitial space. Although 99mTc-DTPA and inuiin clearly diffuse at different rates across the endothelium, as would be expected from their disparate sizes, the similarity in the time courses of their initial exponentials and simultaneous equalization of transfer rates (i.e. when net extraction fraction was zero) is consistent with the hypothesis that inuiin moves initially into a smaller functional interstitial fluid volume than 99mTc-DTPA. The total distribution volumes, however, are not significantly different between the two solutes.

scholarly journals Altered reabsorption of protein by the renal cortex in rats treated with hypertonic saline or mannitol.

1975 ◽  
Vol 23 (10) ◽  
pp. 707-721 ◽  
Author(s):  
W Straus
Keyword(s):  
Acid Phosphatase ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Hypertonic Saline ◽  
Intravenous Injection ◽  
Plasma Clearance ◽  
Renal Cortex ◽  
Proximal Tubule Cells ◽  
Subcutaneous Injections ◽  
Tubule Cells

The reabsorption of horseradish peroxidase (HRP) by the proximal tubule cells of rat kidneys was investigated by measuring the concentration of HRP in total particulate fractions of the cortex 1/4 and 1 hr after intravenous injection, and by correlated cytochemical observations. When compared to the corresponding values of the control animals, the concentration of HRP 1 hr after injection was decreased approximately 10-fold in the renal cortex of rats which had received an intravenous injection of hypertonic saline or two subcutaneous injections of mannitol. The plasma clearance and the urinary excretion of HRP were not altered significantly after injection of hypertonic saline, but the plasma clearance was decreased and the urinary excretion increased after injection of mannitol. When the dose of injected HRP was varied, the reabsorption of HRP by the renal cortex was proportional to the dose in the experimental and the control animals. Cytochemical staining for peroxidase activity also showed that the phagosomes and phagolysosomes of the proximal tubule cells contained much less peroxidase in the experimental rats than in the control rats. After injection of mannitol, large vacuoles appeared in the proximal tubule cells. The vacuoles often contained peroxidase-positive granules (phagosomes) which varied in diameter from the limit of microscopic visibility up to several microns. Most of the vacuoles did not react for acid phosphatase activity, but lysosomes were often aggregated around the vacuoles and seemed to release acid phosphatase into the cytoplasm. Certain analogies between the reabsorption of protein and that of water by the proximal tubule cells are discussed.

scholarly journals Measurement of Cerebral Blood Flow in the Rat with Intravenous Injection of [11C]Butanol by External Coincidence Counting: A Repeatable and Noninvasive Method in the Brain

1984 ◽  
Vol 4 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Shigeharu Takagi ◽  
Kazumasa Ehara ◽  
Peter J. Kenny ◽  
Ronald D. Finn ◽  
Paresh J. Kothari ◽  
...  
Keyword(s):  
Blood Flow ◽  
Rat Brain ◽  
Intravenous Injection ◽  
Regression Line ◽  
Oxygen Extraction Fraction ◽  
Minimum Loss ◽  
Coincidence Counting ◽  
Extraction Fraction ◽  
The Brain ◽  
Large Vessels

No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting (CBFo) from 1-min data and with the recirculation corrected height/area method from 3-min data (CBFh · 3min) and 5-min data (CBFh · 5min). CBFo agreed well with CBFh · 5min, although a slight overestimation was observed in CBFh · 3min. The normal CBFo in the normocapnic group (n = 6, paco2 36.7 ± 2.3 mm Hg) was 1.76 ± 0.49 ml/g min (mean ± SD). A good correlation was observed between CBFo ( y) and Paco2 ( x), and the regression line was y = 0.0629 x – 0.715 (r = 0.88, p < 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (<0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.

Non-Invasive Measurement of Microvascular Permeability to a Small Solute in Man: Validation of the Technique

1995 ◽  
Vol 89 (2) ◽  
pp. 191-200 ◽  
Author(s):  
C. Cousins ◽  
N. D. Jonker ◽  
L. M. Banks ◽  
S. Mohammadtaghi ◽  
M. J. Myers ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Interstitial Fluid ◽  
Extracellular Fluid ◽  
Microvascular Permeability ◽  
Invasive Technique ◽  
Retention Function ◽  
Deconvolution Analysis ◽  
Intravenous Injections ◽  
Non Invasive ◽  
Arterial Blood

1. The purpose of the study was to evaluate a non-invasive technique for measurement of microvascular permeability to a small hydrophilic solute. 2. The technique measures the clearance of 99mTc-labelled diethylenetriaminepenta-acetic acid (99mTc-DTPA) from plasma into interstitial fluid in a limb after intravenous injection and uses a scintillation probe and a technique of graphical analysis called the Patlak plot, the uptake constant of which reflects 99mTc-DTPA transfer from plasma to interstitial fluid. Using deconvolution analysis, the retention function in the limb of intravenous 99mTc-DTPA was also measured. 3. The clearance values given by these two analytical techniques were compared with clearance from the same vascular bed after bolus femoral intra-arterial injection of 99mTc-DTPA. 4. Sixteen patients undergoing routine diagnostic arteriography were studied: six received sequential femoral intra-arterial injections of 99mTc-labelled human serum albumin (HSA) and 99mTc-DTPA, two received sequential intra-arterial and intravenous injections of 99mTc-HSA and eight received sequential intra-arterial and intravenous injections of 99mTc-DTPA. Tissue uptake and clearance were recorded from the limb with a scintillation probe and plasma clearance by arterial blood sampling. Tracer recirculation was addressed using a second scintillation probe over the contralateral limb. 5. After intra-arterial injection, 99mTc-HSA clearance was monoexponential, reflecting intravascular transit, and was completed by 2–5 min in seven subjects and in about 10 min in one. The corresponding 99mTc-DTPA clearance curves in the six subjects who also received intra-arterial DTPA were biexponential, analysis of which yielded a 99mTc-DTPA extraction fraction of about 0.6. By comparison with 99mTc-HSA clearance, the first exponential clearly corresponded to intravascular transit of unextracted 99mTc-DTPA. 6. In the eight patients given sequential intra-arterial and intravenous injections of 99mTc-DTPA, the second exponential recorded after intra-arterial injection, representing 99mTc-DTPA clearance from the interstitial fluid, agreed well with (a) the Patlak uptake constant recorded over the limb after intravenous injection, representing clearance from plasma into the interstitial fluid and (b) the retention function of 99mTc-DTPA in a limb calculated by deconvolution analysis. The mean clearance following intraarterial injection (expressed in relation to extracellular fluid volume) was 9.6 (SD 2.4) ml min−1 100 ml−1, while the corresponding mean clearance after intravenous injection was 8.8 (2.1) ml min−1 100 ml−1 calculated by Patlak analysis and 10.5 (2.7) ml min−1 100 ml−1 by deconvolution analysis. 7. We conclude that, under the conditions of measurement, 99mTc-DTPA is about 60% extracted into the interstitial fluid in a single pass through an extremity and that clearance into the extravascular space can be measured with reasonable accuracy after intravenous injection.

The vagus nerve in the thermoregulatory response to systemic inflammation

1997 ◽  
Vol 273 (1) ◽  
pp. R407-R413 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. T. Simons ◽  
M. Szekely ◽  
V. A. Kulchitsky
Keyword(s):  
Intravenous Injection ◽  
Systemic Inflammation ◽  
Second Phase ◽  
Thermoregulatory Response ◽  
Cool Environment ◽  
Bolus Intravenous Injection ◽  
High Doses ◽  
Colonic Temperature ◽  
Dose Dependent ◽  
Higher Doses

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.

scholarly journals Appropriate background correction for DTPA aerosol clearance

1998 ◽  
Vol 84 (3) ◽  
pp. 1103-1107 ◽  
Author(s):  
G. R. Mason ◽  
A. M. Peters ◽  
M. J. Myers ◽  
J. M. B. Hughes
Keyword(s):  
Background Subtraction ◽  
Time Course ◽  
Gas Barrier ◽  
Time Activity ◽  
Lung Clearance ◽  
Pulmonary Capillary ◽  
Distal Airway ◽  
True Shape ◽  
Convex Upward ◽  
Time Courses

Measurement of the clearance rate of inhaled aerosols of99mTc-diethylenetriamine pentaacetic acid (DTPA) from distal airway to pulmonary capillary is a sensitive technique for the detection of lung injury. As the solute diffuses across the blood-gas barrier, the concentration in circulating blood increases, giving rise to a background signal superimposed on the signal from residual DTPA in the airway. Background subtraction is conventionally based on the thigh, but this tissue has the disadvantage in that its composition, in terms of the relative volumes of its extracellular extravascular and intravascular compartments (a ratio of ∼4:1), is quite different from that of the lung (<1:6). With comparison to the thigh, we examined alternative regions for background, liver, and cranium, which have extravascular-to-intravascular compartment ratios much closer to these for the lung, to determine the most appropriate background for correction of the pulmonary signal. From 1 min after intravenous injection of 99mTc-DTPA, the time-activity curves recorded by a gamma camera over the liver and lung in a group of otherwise normal cigarette smokers decreased up to 30 min after injection, with time courses that could essentially be superimposed on each other; the curve recorded over the thigh with a separate scintillation probe continued to increase. The curve recorded over the cranium had a time course similar to that for the liver and lung. Following aerosol inhalation, the lung clearance rates over the initial 7 min when background subtraction was used, based on the liver, cranium, and thigh were, respectively, 4.9 ± 2.9, 4.7 ± 2.6, and 5.4 ± 3.4 (SD) %/min, compared with 4.1 ± 2.2%/min without subtraction. The corresponding values based on 30 min of data were 3.3 ± 1.4, 3.4 ± 1.4, 4.2 ± 2.3, and 2.8 ± 1.0%/min. When the liver was used for background, the lung clearance curves were clearly multiexponential, whereas thigh correction tended to give curves that were monoexponential or even convex upward on semilogarithmic axes. With an appropriate region for background, the true shape of a lung curve can be identified, which permits the study of an intervention on the clearance while it is in progress. The intravenous DTPA, required for calibrating the background regions, can be given before inhalation of the tracer.

scholarly journals Kinetic Analysis of [11C]McN5652: A Serotonin Transporter Radioligand

1999 ◽  
Vol 19 (9) ◽  
pp. 967-981 ◽  
Author(s):  
Zsolt Szabo ◽  
Ursula Scheffel ◽  
William B. Mathews ◽  
Hayden T. Ravert ◽  
Katalina Szabo ◽  
...  
Keyword(s):  
Impulse Response ◽  
Response Function ◽  
Serotonin Transporter ◽  
Quantitative Estimation ◽  
Impulse Response Function ◽  
Nonspecific Binding ◽  
Time Activity ◽  
Deconvolution Analysis ◽  
Tissue Compartment ◽  
Regional Cerebral Blood Volume

The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)-McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](–)-McN5652. The impulse response function was calculated by deconvolution analysis of regional time–activity curves, and its peak value ( fmax), its retention value at 75 minutes ( fT), and its normalized retention ( frel = fT/ fmax) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume ( DVT) and its specific binding component ( DVs). Both the noncompartmental ( fT, frel) and the compartmental parameters ( DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](–)-McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance–covariance matrix was the one that was based on a single tissue compartment with parameters k1 and k2 and that also included the parameter of regional cerebral blood volume ( BV). The parameter frel demonstrated low between-subject variance (coefficient of variation [ CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT ( r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, frel demonstrated further improvement in correlation ( r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform ln DV was used instead of DV (17% for the three-parameter model), but correlation of this compartmental parameter was slightly less ( r = 0.652 for the three-parameter model) than the correlation of the noncompartmental frel with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive enantiomer ( r = 0.694; CV = 22%). These results indicate that the kinetics of [11C](+)McN5652 can best be described by a one-tissue compartment model with three parameters ( k1, k2, and BV), and that both the noncompartmental parameter frel and the compartmental distribution volumes have the potential for quantitative estimation of the density of SERT. Further validation of the radioligand in experimental and clinical situations is warranted.

Effects of insulin on hexose transport across blood-brain barrier in normoglycemia

1987 ◽  
Vol 252 (3) ◽  
pp. E299-E303 ◽  
Author(s):  
H. Namba ◽  
G. Lucignani ◽  
A. Nehlig ◽  
C. Patlak ◽  
K. Pettigrew ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Rate Constants ◽  
Time Course ◽  
Brain Barrier ◽  
Tissue Concentrations ◽  
Arterial Blood ◽  
Blood Brain ◽  
Measured Time ◽  
Time Courses ◽  
Arterial Plasma

The effects of insulin on 3-O-[14C]methylglucose transport across the blood-brain barrier (BBB) were studied in conscious rats under steady-state normoglycemic conditions. The [14C]methylglucose was infused intravenously at a constant rate, and animals were killed at various times between 5 and 30 min after the initiation of the infusion. The time course of the arterial plasma concentration of [14C]methylglucose was determined in timed arterial blood samples taken during the infusion. Local cerebral tissue concentrations of [14C]methylglucose at the time of killing were determined by quantitative autoradiography of brain sections. The rate constants for inward and outward transport of [14C]methylglucose across the BBB, K1, and k2, respectively, were estimated by a least-squares, best-fit of a kinetic equation to the measured time courses of plasma and tissue concentrations. K1 and k2 were reduced by an average of 24 and 31%, respectively, in gray matter and 7 and 16% in white matter from values estimated similarly in normal insulinemic control rats. The equilibrium distribution ratio, K1/k2, for [14C]methylglucose in brain increased by approximately 10–11% in the hyperinsulinemic animals. Because 3-O-[14C]methylglucose shares the same carrier that transports glucose and other hexoses across the BBB, these results suggest that hyperinsulinemia decreases the rate constants for transport but increases the distribution space for hexoses in brain. These effects are, however, quite small and are probably minor or negligible when compared with the major effects of insulin in other tissues.

Renal Release of Active and Inactive Renin in Essential and Renovascular Hypertension

1978 ◽  
Vol 55 (s4) ◽  
pp. 129s-132s ◽  
Author(s):  
F. H. M. Derkx ◽  
R. P. Verhoeven ◽  
G. J. Wenting ◽  
A. J. Man in 't Veld ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Essential Hypertension ◽  
Renovascular Hypertension ◽  
Intravenous Injection ◽  
Renal Vein ◽  
Active Renin ◽  
A Value ◽  
Affected Side ◽  
Inactive Renin ◽  
Arterial Plasma

1. Active and acid-activable inactive renin were measured in renal venous and arterial plasma of 18 patients with essential hypertension (EHT) and 19 patients with renovascular hypertension (RVHT). In seven patients with EHT and in 11 patients with RVHT measurements were made before and 25–35 min after an intravenous injection of 300 mg of diazoxide. 2. Under basal conditions the renal vein to artery ratios for active and inactive renin in EHT ranged from 0·71 to 1·96 and from 0·68 to 1·44 respectively. In 14 patients with RVHT the renal vein to artery ratio for active renin on the affected side was above the range found in EHT and in six of them the renal vein to artery ratio for inactive renin was also elevated. 3. The diazoxide-induced release of active renin from kidneys, which had a stenotic artery but were not seriously contracted, was associated with a fall of the renal vein to artery ratio for inactive renin to a value below 1·00. 4. The results indicate that changes in the release of active and inactive renin do not always run in parallel. The findings are compatible with the hypothesis that circulating inactive renin can be activated in the kidney.

Studies in sheep examining plasma follistatin elevations due to frequent blood sampling or surgery

1996 ◽  
Vol 8 (2) ◽  
pp. 273 ◽  
Author(s):  
R Klein ◽  
DM Robertson ◽  
IJ Clarke
Keyword(s):  
Intravenous Injection ◽  
Plasma Clearance ◽  
Blood Sampling ◽  
Induced Response ◽  
Tetraacetic Acid ◽  
Before And After ◽  
Bolus Intravenous Injection ◽  
Per Se ◽  
Frequent Sampling ◽  
Elevate Plasma

This study examined the effects of the anticoagulant heparin on plasma follistatin (FS) concentrations used during blood sampling in Corriedale ewes. Plasma FS concentrations increased acutely (P < 0.01) following a bolus intravenous injection of heparin (3200 U). To determine whether frequent sampling per se can also increase plasma FS concentrations, ewes were sampled using a substitute anticoagulant, ethylenediamine tetraacetic acid. Frequent sampling had no effect on plasma FS concentrations. alpha-2 Macroglobulin concentrations were measured before and after bilateral ovariectomy and sham ovariectomy to determine whether this agent causes an increase in plasma FS concentrations 10-12 h after laparotomy. No differences in plasma alpha-2 macroglobulin concentrations were observed at the time of the observed increase in plasma FS concentrations. In conclusion: (1) heparin caused acute elevations in plasma FS concentrations probably by binding to FS, thereby reducing its plasma clearance; (2) rapid blood sampling per se did not elevate plasma FS concentrations; (3) alpha-2 macroglobulin concentrations were not elevated at the same time as plasma FS concentrations 10-12 h after surgery; and (4) the small increase in alpha-2 macroglobulin concentrations before surgery was attributable to a stress-induced response as seen in other species.

Sign in / Sign up

Export Citation Format

Share Document