Validation of a single-compartment approach to the calculation of secretion rates of ACTH

1978 ◽  
Vol 56 (3) ◽  
pp. 410-415 ◽  
Author(s):  
John S. Cowan

A single-compartment model used in this laboratory for continuously calculating ACTH secretion rates from measured plasma ACTH concentrations has been tested for its ability to follow changing rates of ACTH entry (rapid departure from steady state). ACTH was infused at known moderately high but physiological rates into anaesthetized dogs (Nembutal). Under such conditions endogenous secretion is initially <5% of infused rates. Orthogonal polynomials (ACTHt) were fitted to plasma ACTH vs. time data. Then [Formula: see text] where it was previously shown that the metabolic clearance rate of ACTH (MCR) lacked significant inter-animal or concentration-dependent variation, and its distribution volume (V) was also constant.The calculated ACTH entry rate curves (a) followed a 10-fold increase in infusion rate over 4 min and subsequent rapid decline with a lag of only about 1 min and, despite some blurring, gave an integrated response equal to 94 ± 5.5% of the known signal, and (b) followed a sinusoidal change in infusion rate (amplitude, 1.7 × base rate; period, 40 min) with a few percent error and negligible lag. These signals imitate (a) an abrupt stress response, and (b) other rapid departures from steady state.

1986 ◽  
Vol 251 (2) ◽  
pp. R365-R370 ◽  
Author(s):  
A. M. Moses ◽  
E. Steciak

Synthetic arginine vasopressin (AVP) was infused into 11 hydrated normal subjects at five different infusion rates ranging from 10 to 350 microU X kg-1 X min-1. Each infusion rate was continued for 1 h, and urinary determinations were made on the 30- to 60-min specimens during which time there was no further rise in plasma AVP. Urinary AVP concentrations (microU/ml) and excretion rates (microU/min) increased linearly with increasing infusion rates, and the concentration of AVP in urine increased 120 times more rapid than plasma. Urinary and metabolic clearances of AVP also increased linearly with the maximum urinary clearance being 60.6% of the creatinine clearance. The total metabolic clearance of AVP (including urinary clearance) was 17.8 times that of the urinary clearance of AVP alone. These data clarify the relationships between plasma and urinary AVP in normal hydrated subjects during AVP infusion under steady-state conditions and emphasize the potential advantage of measuring urinary AVP as a monitor of endogenous AVP secretion.


1984 ◽  
Vol 246 (3) ◽  
pp. R325-R330
Author(s):  
O. P. McGuinness ◽  
J. J. Spitzer

The metabolic clearance rate (MCR) and maximal rate of glycerol removal (Rd max) were determined in anesthetized dogs at two time periods after the intravenous administration of either Escherichia coli endotoxin or saline. The nonisotopic method employed in these studies to determine the MCR of glycerol consisted of a constant infusion of glycerol at three different infusion rates. At each infusion rate a steady-state glycerol concentration was obtained. The reciprocal of the slope of the linear relationship between the glycerol infusion rate and the change in the steady-state arterial glycerol concentration was equal to the MCR of glycerol. Administration of endotoxin significantly decreased the MCR of glycerol, whereas the volume of distribution of glycerol was not altered significantly. The arterial glycerol turnover remained unaltered, whereas arterial glycerol concentration increased after endotoxin administration. The studies demonstrate that the elevated arterial glycerol concentration maintained the rate of glycerol turnover in the face of decreased efficiency of glycerol removal after endotoxin administration.


1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand

The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40–2560 μU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalarno–pituitary–adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.


1979 ◽  
Vol 92 (3) ◽  
pp. 489-501 ◽  
Author(s):  
O. Spira ◽  
A. Birkenfeld ◽  
J. Gross ◽  
A. Gordon

ABSTRACT Groups of surgically thyroidectomized (T) male rats were sacrificed at intervals during the period of 1 to 5 and 30 to 180 days after <UNK> Plasma T3, T4 and TSH levels and pituitary TSH content were measured by RIA. A drop of plasma T3 and T4 from normal to undetectable values occurred by day 3 post <UNK>. There was a progressive increase of plasma TSH from the normal value of 136 ± 14 ng/ml to 1623 ± 186 ng/ml (mean ± sem) at day 5 post T, reaching at 30 days a new plateau of 8618 ± 527 ng/ml. These levels remained unchanged up to 130 days post <UNK>. At 180 days, plasma TSH (4123 ± 991 ng/ml) fell significantly below the plateau level. Pituitary TSH content fell from the normal value of 80.9 ± 15.9 μg/mg to a nadir of 12.7 ± 1.4 μg/mg at day 4 post <UNK> and then slowly rose to 98.6 ± 5.9 μg/mg at 100 days, remaining at this level for another 30 days and finally declining significantly at 180 days post <UNK>. The rates of TSH release and synthesis were calculated using the metabolic clearance rates (MCR), determined from the curves of disappearance of injected [125I]-TSH by a non-compartmental analysis. The MCR values decreased, starting at 8 days after T, and reached about half the normal value from 30 days onwards (0.257 ± 0.03 to 0.144 ± 0.001 ml/min/100 g b.w.). The rate of TSH release was increased as early as the first day post <UNK>. A 6-fold increase was reached after 5 days and a new steady state of about 32-fold increase was attained within 1 month. TSH synthesis was also stimulated. However, it lagged behind the stimulation of the release for the first 4 days after <UNK>. The data indicate that: a) The depletion of thyroid hormones affects both synthesis and release of TSH. b) Under prolonged hypothyroidism TSH release and synthesis are in equilibrium, at a markedly enhanced rate. c) Very severe and prolonged hypothyroidism results in a decline in both pituitary and plasma TSH levels.


1981 ◽  
Vol 97 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Th. Lemarchand-Béraud ◽  
C. Berthier

Abstract. The effects of a graded low dose of T3 on plasma TSH, anterior pituitary TSH content (AP-TSH) and on TSH synthesis and secretion rates, were studied in adult male rats previously treated for 7 days with 0.01% prophylthiouracil (PTU). Pituitary TSH content, plasma T3, T4 and TSH levels were measured by RIA at 0, 6, 12, 24 h after the injection of T3 ranging from 0.1 to 0.75 μg/100 g b.w. Saline treated normal rats served as control. The 7-day PTU treated rats displayed low but still detectable thyroid hormone plasma levels; high plasma TSH levels were observed, but with no further increase after TRH injection as the AP-TSH content was depleted. Injections of T3 increased plasma T3 in proportion with the dose given. Plasma T4 remained low and there was no significant decrease in plasma TSH until doses of 0.2 μg/100 g b.w. T3 was given. Then the transient TSH depression was dose-dependent from 0.2 to 0.75 μg/100 g b.w. The AP-TSH content increased regularly from 0.2 μg/T3 onwards, overlapping the transient inhibition of TSH secretion resulting in a 3-fold increase in the AP-TSH content, suggesting a positive action of T3 on TSH synthesis. In addition, TSH response to TRH was observed at every time studied after T3 injection. Then, the different groups were injected with [125I]rTSH in order to estimate metabolic clearance rates, TSH secretion and synthesis rates. The half-life of [125I]rTSH (22 min) and its metabolism clearance rates (16 ± 0.4 ml/h/100 g b.w.) were found similar in all groups. Whereas the TSH secretion rates was highly reduced in the normal rats receiving 0.3 μg T3 (156 ± 9 vs 408 ± 22 μg/24 h in normal rats), the PTU group displayed a 3-fold increased secretion rate (1222 ± 44 μg/24 h) which was not modified by the injection of 0.1–0.2 μg T3 and decreased to 868 and 472 μg/24 h with 0.3 μg and 0.75 μg T3, respectively. TSH synthesis rates were found highly increased in the PTU group (1222 ± 44 μg/d vs 408 ± 22 μg/d in normal rats) and was neither increased nor reduced in the 7-day PTU rats receiving 0.1–0.3 μg T3 but a slight reduction was observed only in the 0.75 μg T3 group. These data show that 0.1–0.2 μg/100 g b.w. T3 changed neither TSH secretion nor its synthesis rates while 0.3 μg more or less a replacement dose inhibited TSH secretion without changing TSH synthesis rates, resulting in a AP-TSH replenishment. Therefore, no direct positive effect of low doses of T3 on TSH synthesis could be demonstrated over 24 h while higher doses are capable of inhibiting first secretion and then synthesis of TSH.


1975 ◽  
Vol 53 (4) ◽  
pp. 592-602 ◽  
Author(s):  
John S. Cowan

The metabolic clearance rate (MCR) for ACTH in adult dogs was previously shown not to vary significantly with varying plasma ACTH concentrations or among dogs. This is confirmed here for pups aged 1–7 days. Hence, ACTH secretion rates can be continuously calculated from a continuous function of plasma ACTH vs. time. Each of seven adult dogs under Nembutal anesthesia received two or three intravenous (i.v.) injections of histamine with increasing doses. The first injections in each dog ranged from 7 to 50 μg/kg, while the last dose was 62–108 μg/kg. A total of 16 injections were given. Twelve pups (two litters of six) aged 1–7 days each received one injection of histamine of 76–116 μg/kg (i.v.). ACTH concentrations in plasma were determined by an adrenal cell suspension bioassay before, and 6 times after each injection. Nine pups also underwent determinations of their MCR for ACTH, with plateau concentrations determined at three times during an ACTH infusion. Continuous curves of ACTH secretion rates were calculated for all 28 histamine injections, showing that all except the 1-day-old pups secrete considerable ACTH when stressed. Compared to adult dogs, the pups show lower secretion rate peaks and shorter periods of rapid secretion. Changes in plasma glucocorticoids also suggest that the adrenal cortex of newborn dogs can respond to ACTH by increased glucocorticoid secretion.


1984 ◽  
Vol 62 (2) ◽  
pp. 199-207 ◽  
Author(s):  
John S. Cowan ◽  
Penney Gaul ◽  
Bruce C. Moor ◽  
Jacob Kraicer

In 28 6-h experiments on 10 conscious resting trained male dogs, plasma growth hormone (GH) was determined at 5-min intervals by radioimmunoassay. For all experiments, the basal GH concentration in plasma was 0.80 ± 0.06 ng mL−1. In each experiment, 1–3 secretory bursts of GH occurred, raising plasma GH 2.4 to 15.3 times basal concentrations (for all 43 bursts, 6.6 ± 0.4 times the basal value). Metabolic clearance rates (MCR) and apparent distribution volumes (V) were determined, using stepwise infusions of canine GH. The MCR (3.99 ± 0.30 mL kg−1 min−1) and V (57.9 ± 5.5 mL kg−1) were used to transform the GH concentration versus time data into GH secretion rates, using a single compartment approach. Basal GH secretion rates for all 28 experiments were 3.12 ± 0.24 ng kg−1 min−1. The secretory bursts yield peak GH secretion rates of 9.4 ± 0.8 times basal secretion and these steep-sloped bursts last 25.1 ± 1.2 min. Six-hour infusions of 0.15 μg kg−1 min−1 of somatostatin (SRIF) abolished all secretory bursts but did not lower basal secretion rates. In five of seven SRIF infusion experiments in which samples were taken after the infusion ceased a secretory burst was seen in the hour following cessation of infusion (in four cases within 10 min). These secretory bursts lasted 23.0 ± 2.9 min and were similar to those seen in control experiments. Infusions of SRIF at 0.05 μg kg−1 min−1 had no effect. These results imply that during basal GH secretion, a surfeit of SRIF impinges on the somatotrophs, as extra SRIF does not further lower basal secretion. However, during secretory bursts, very little SRIF must be present, as exogenous SRIF blocks these bursts. The bursts are similar in duration to overshoots provoked in perifused dispersed rat somatotrophs by removal of an SRIF signal. It seems likely that their cause in vivo is similar. (All values are means ± SEM.)


1997 ◽  
Vol 36 (04/05) ◽  
pp. 368-371
Author(s):  
R. Soma ◽  
Y. Yamamoto

Abstract.A new method was developed for continuous isotopic estimation of human whole body CO2 rate of appearance (Ra) during non-steady state exercise. The technique consisted of a breath-by-breath measurement of 13CO2 enrichment (E) and a real-time fuzzy logic feedback system which controlled NaH13CO3 infusion rate to achieve an isotopic steady state. Ra was estimated from the isotope infusion rate and body 13CO2 enrichment which was equal to E at the isotopic steady state. During a non-steady state incremental cycle exercise (5 w/min or 10 w/min), NaH13CO3 infusion rate was successfully increased by the action of feedback controller so as to keep E constant.


1961 ◽  
Vol 38 (3) ◽  
pp. 469-472 ◽  
Author(s):  
K. R. Laumas ◽  
J. F. Tait ◽  
S. A. S. Tait

ABSTRACT Reconsideration of the question of the validity of the calculations of the secretion rates from the specificity activity of a urinary metabolite after the single injection of a radioactive hormone has led us to conclude that the basic equations used in a previous theoretical treatment are not generally applicable to the nonisotopic steady state if the radioactive steroid and hormone are introduced into the same compartment. If this is so, in a two compartmental model with metabolism occurring in both pools, it is now shown that the calculation (S = R — τ) is rigorously valid if certain precautions are taken. This is in contrast to the previous treatment which concluded (in certain special circumstances) that the calculation might not be correct. However, if the hormone is secreted in both compartments and the radioactive steroid is injected into only one, then the calculation (S = R — τ) may not be correct in certain circumstances as was previously concluded (Laumas et al. 1961).


1999 ◽  
Vol 2 (03) ◽  
pp. 271-280 ◽  
Author(s):  
Ekrem Kasap ◽  
Kun Huang ◽  
Than Shwe ◽  
Dan Georgi

Summary The formation-rate-analysis (FRASM) technique is introduced. The technique is based on the calculated formation rate by correcting the piston rate with fluid compressibility. A geometric factor is used to account for irregular flow geometry caused by probe drawdown. The technique focuses on the flow from formation, is applicable to both drawdown and buildup data simultaneously, does not require long buildup periods, and can be implemented with a multilinear regression, from which near-wellbore permeability, p * and formation fluid compressibility are readily determined. The field data applications indicate that FRA is much less amenable to data quality because it utilizes the entire data set. Introduction A wireline formation test (WFT) is initiated when a probe from the tool is set against the formation. A measured volume of fluid is then withdrawn from the formation through the probe. The test continues with a buildup period until pressure in the tool reaches formation pressure. WFTs provide formation fluid samples and produce high-precision vertical pressure profiles, which, in turn, can be used to identify formation fluid types and locate fluid contacts. Wireline formation testing is much faster compared with the regular pressure transient testing. Total drawdown time for a formation test is just a few seconds and buildup times vary from less than a second (for permeability of hundreds of millidarcy) to half a minute (for permeability of less than 0.1 md), depending on system volume, drawdown rate, and formation permeability. Because WFT tested volume can be small (a few cubic centimeters), the details of reservoir heterogeneity on a fine scale are given with better spatial resolution than is possible with conventional pressure transient tests. Furthermore, WFTs may be preferable to laboratory core permeability measurements since WFTs are conducted at in-situ reservoir stress and temperature. Various conventional analysis techniques are used in the industry. Spherical-flow analysis utilizes early-time buildup data and usually gives permeability that is within an order of magnitude of the true permeability. For p* determination, cylindrical-flow analysis is preferred because it focuses on late-time buildup data. However, both the cylindrical- and spherical-flow analyses have their drawbacks. Early-time data in spherical-flow analysis results in erroneous p* estimation. Late-time data are obtained after long testing times, especially in low-permeability formations; however, long testing periods are not desirable because of potential tool "sticking" problems. Even after extended testing times, the cylindrical-flow period may not occur or may not be detectable on WFTs. When it does occur, permeability estimates derived from the cylindrical-flow period may be incorrect and their validity is difficult to judge. New concepts and analysis techniques, combined with 3-D numerical studies, have recently been reported in the literature.1–7 Three-dimensional numerical simulation studies1–6 have contributed to the diagnosis of WFT-related problems and the improved analysis of WFT data. The experimental studies7 showed that the geometric factor concept is valid for unsteady state probe pressure tests. This study presents the FRA technique8 that can be applied to the entire WFT where a plot for both drawdown and buildup periods renders straight lines with identical slopes. Numerical simulation studies were used to generate data to test both the conventional and the FRA techniques. The numerical simulation data are ideally suited for such studies because the correct answer is known (e.g., the input data). The new technique and the conventional analysis techniques are also applied to the field data and the results are compared. We first review the theory of conventional analysis techniques, then present the FRA technique for combined drawdown and buildup data. A discussion of the numerical results and the field data applications are followed by the conclusions. Analysis Techniques It has been industry practice to use three conventional techniques, i.e., pseudo-steady-state drawdown (PSSDD), spherical and cylindrical-flow analyses, to calculate permeability and p* Conventional Techniques Pseudo-Steady-State Drawdown (PSSDD). When drawdown data are analyzed, it is assumed that late in the drawdown period the pressure drop stabilizes and the system approaches to a pseudo-steady state when the formation flow rate is equal to the drawdown rate. PSSDD permeability is calculated from Darcy's equation with the stabilized (maximum) pressure drop and the flowrate resulting from the piston withdrawal:9–11 $$k {d}=1754.5\left({q\mu \over r {i}\Delta p {{\rm max}}}\right),\eqno ({\rm 1})$$where kd=PSSDD permeability, md. The other parameters are given in Nomenclature.


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