Changes in glycerol kinetics after E. coli endotoxin administration in dogs

1984 ◽  
Vol 246 (3) ◽  
pp. R325-R330
Author(s):  
O. P. McGuinness ◽  
J. J. Spitzer
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Volume Of Distribution ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Glycerol Concentration ◽  
Endotoxin Administration ◽  
E Coli ◽  
The Face ◽  
Anesthetized Dogs

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.

Assessment of methods for improving tracer estimation of non-steady-state rate of appearance

1999 ◽  
Vol 87 (5) ◽  
pp. 1813-1822 ◽  
Author(s):  
A. Gastaldelli ◽  
A. R. Coggan ◽  
R. R. Wolfe
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Traditional Approach ◽  
Volume Of Distribution ◽  
Constant Volume ◽  
Constant Infusion ◽  
Steady State Condition ◽  
Fixed Volume ◽  
The One ◽  
Infusion Technique

The most common approach for estimating substrate rate of appearance (Ra) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. ( Am. J. Physiol. 187: 15–24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215–224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng ⋅ kg−1 ⋅ min−1) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of Raobtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating Ra for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR1/TTR2approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose Ra can be obtained with the constant-infusion technique if V = 145 ml/kg.

Glucose and lactate kinetics after endotoxin administration in dogs.

1977 ◽  
Vol 232 (2) ◽  
pp. E180 ◽  
Author(s):  
R R Wolfe ◽  
D Elahi ◽  
J J Spitzer
Keyword(s):  
Lactate Concentration ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Plasma Lactate ◽  
Metabolic Clearance Rate ◽  
Metabolic Substrate ◽  
E Coli ◽  
Lactate Kinetics ◽  
Plasma Lactate Concentration

We studied the effects of E. coli endotoxin on the glucose and lactate kinetics in dogs by means of the primed constant infusion of [6(-3)H] glucose and Na-L-(+)-[U-14C] lactate. The infusion of endotoxin induced a transient hyperglycemic level, followed by a steady fall in plasma glucose to hypoglycemic levels. The rate of appearance (Ra) and the rate of disappearance (Rd) of glucose were both significantly elevated (P less than .05) for 150 min after endotoxin, after which neither differed from the preinfusion value. The metabolic clearance rate of glucose was significantly elevated at all times 30 min postendotoxin. By 30 min postendotoxin, Ra and Rd of lactate, plasma lactate concentration, and the percent of glucose turnover originating from lactate were significantly elevated and remained so for the duration of the experiment. We concluded that after endotoxin hypoglycemia developed because of an enhanced peripheral uptake of glucose and a failure of the liver to maintain an increased Ra of glucose. We also concluded that lactate became an important precursor for gluconeogenesis and an important metabolic substrate.

Hyperthyroidism and the Dynamics of Distribution and Renal Excretion of Epinephrine in the Dog

1958 ◽  
Vol 193 (2) ◽  
pp. 375-378 ◽  
Author(s):  
Richard T. Jones ◽  
William D. Blake
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Renal Excretion ◽  
Volume Of Distribution ◽  
Constant Infusion ◽  
Thyroid Extract ◽  
Anesthetized Dogs

Several parameters related to the dynamics of distribution and renal excretion of epinephrine were studied in anesthetized dogs before and during oral administration of thyroid extract. These parameters include: a) plasma concentration and renal excretion of epinephrine during constant infusion of l-epinephrine bitartrate, b) the rate of disappearance from plasma and volume of distribution of epinephrine, and c) the resting excretion of endogenous epinephrine before and during thyroid feeding. Except for an increase in the percentage of infused epinephrine excreted in the urine, there were essentially no changes in these parameters after feeding thyroid.

Relationship between turnover rate and blood concentration of lactate in exercising dogs

1975 ◽  
Vol 39 (2) ◽  
pp. 231-234 ◽  
Author(s):  
F. L. Eldridge
Keyword(s):  
Steady State ◽  
Blood Lactate ◽  
Turnover Rate ◽  
The Other ◽  
Constant Infusion ◽  
Blood Concentrations ◽  
Lactate Turnover ◽  
Anesthetized Dogs ◽  
Lactate Removal ◽  
The Relationship

Steady-state blood lactate concentrationss and lactate turnover, or entry, rates were determined by use of constant infusion of L(+)-[14C]lactate in seven anesthetized dogs before and during electrically induced exercise. Lactate entry rates increased during exercise in all dogs with or without the infusion of additional exogenous cold lactate. Blood lactate concentrations, on the other hand, rose to levels considerably below those predicted for these entry rates in a previous study of the relationship in normal nonexercising dogs. It is concluded that improved efficiency of lactate removal during exercise allows low blood concentrations despite large increases in entry rates.

scholarly journals The Role of Pharmacokinetics in Anaesthesia: Application to Intravenous Infusions

1987 ◽  
Vol 15 (1) ◽  
pp. 7-14 ◽  
Author(s):  
D. R. Stanski
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
Metabolic Clearance ◽  
Drug Infusion ◽  
Fixed Rate ◽  
Elimination Half

Pharmacokinetic concepts describe the relationship between drug dose and resulting plasma concentration. A drug's pharmacokinetic profile can be described by distribution and elimination half-lives, initial volume of distribution, steady-state distribution volume, and metabolic and distributional clearance. After initiating a fixed rate of drug infusion, four to five terminal elimination half-lives are required to reach a steady state of constant plasma concentration. If a loading dose is given, a steady state can be achieved more rapidly. The most rapid method of achieving a constant plasma concentration involves using a variable rate of drug infusion that adjusts for the metabolic clearance and distribution of the drug. Computer-driven infusion pumps can be used to rapidly achieve, then maintain, constant plasma concentrations of a drug.

Urinary and metabolic clearances of arginine vasopressin in normal subjects

1986 ◽  
Vol 251 (2) ◽  
pp. R365-R370 ◽  
Author(s):  
A. M. Moses ◽  
E. Steciak
Keyword(s):  
Steady State ◽  
Creatinine Clearance ◽  
Arginine Vasopressin ◽  
Infusion Rate ◽  
Normal Subjects ◽  
Metabolic Clearance ◽  
Excretion Rates

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.

Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism.

1978 ◽  
Vol 235 (6) ◽  
pp. E591 ◽  
Author(s):  
R E Weitzman ◽  
D A Fisher
Keyword(s):  
Arginine Vasopressin ◽  
Urine Osmolality ◽  
Volume Of Distribution ◽  
Membrane Receptors ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Strong Negative Correlation ◽  
Pulse Injection ◽  
Plasma Membrane Receptors ◽  
Infusion Technique

The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.

Influence of nephrectomy on the glucoregulatory response to insulin administration in the rat

1980 ◽  
Vol 58 (3) ◽  
pp. 301-305 ◽  
Author(s):  
Gavino Perez ◽  
Giacomo Carteni ◽  
Biagio Ungaro ◽  
Luigi Saccà
Keyword(s):  
Plasma Concentrations ◽  
Insulin Injection ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
The Face ◽  
Plasma Insulin Levels ◽  
Glucagon And Insulin ◽  
Glucose Output

Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon and insulin, it was possible to assess the tissue sensitivity to physiologic and supraphysiologic levels of these two hormones and the site of insulin resistance. The effect of an intravenous injection of insulin (100 mU) on glucose turnover was studied in acutely uremic rats 15 h after bilateral nephrectomy and in sham-operated controls, in the postabsorptive state. Glucose output by the liver and uptake by tissues were determined by the primed constant infusion technique using [3-3H]glucose. Under basal conditions, no significant differences in Ra and Rd between the two groups were observed, while a significant hyperglycemia and a reduced glucose metabolic clearance rate in the face of hyperglucagonemia and normal plasma insulin levels were observed in nephrectomized rats. After insulin injection, the glycemic curves were similar in the two groups, while Ra, Rd, and MCR displayed significantly lower values in nephrectomized rats in the face of higher plasma concentrations of insulin and glucagon. It was concluded that acute uremia in the rat is characterized by a loss of the normal ability of insulin to promote peripheral glucose uptake with retention of hepatic sensitivity to insulin.

Non-insulin-mediated glucose uptake predominates in postabsorptive dogs

1987 ◽  
Vol 252 (5) ◽  
pp. E660-E666 ◽  
Author(s):  
M. Lavelle-Jones ◽  
M. H. Scott ◽  
O. Kolterman ◽  
A. R. Moossa ◽  
J. M. Olefsky
Keyword(s):  
Steady State ◽  
Glucose Uptake ◽  
Serum Insulin ◽  
Glucose Disposal ◽  
High Dose ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Assay Sensitivity ◽  
Endogenous Insulin ◽  
Anesthetized Dogs

Overall glucose uptake represents the sum of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). In this study, we compared the rate of NIMGU in conscious and anesthetized dogs. Rates of glucose disposal were compared in the basal state and during severe insulinopenia after endogenous insulin suppression by high-dose somatostatin (SRIF) infusion. Steady-state NIMGU rates were calculated 2 h after commencing SRIF infusion. Three groups of studies were performed: 1) SRIF in conscious dogs; 2) SRIF in anesthetized dogs; and 3) SRIF plus glucagon, also in anesthetized dogs. In all three groups, serum insulin levels were reduced to below assay sensitivity after SRIF infusion. The basal metabolic clearance rate of glucose (MCRg) for each group was 3.8 +/- 0.4, 3.6 +/- 0.3, and 3.6 +/- 0.3 ml X kg-1 X min-1, respectively (P = NS, all groups). Steady-state NIMGU rates were 2.4 +/- 0.2 (conscious), 2.5 +/- 0.1 (anesthetized, SRIF only), and 2.4 +/- 0.1 ml/kg/min (anesthetized, SRIF plus glucagon). Thus, absolute rates of NIMGU expressed as MCRg in conscious and anesthetized animals do not differ and in the three groups studied comprise approximately the same proportion of the basal glucose uptake (approximately 64, approximately 69, and approximately 66%, respectively). We conclude that approximately 66% of basal postabsorptive glucose uptake occurs via NIMGU mechanisms and that this pathway is unaffected by anesthesia and surgery.

Renal concentrating operation in hypothermic dogs

1959 ◽  
Vol 196 (5) ◽  
pp. 1150-1154 ◽  
Author(s):  
Suk Ki Hong ◽  
John W. Boylan
Keyword(s):  
Steady State ◽  
Body Temperature ◽  
Isotonic Saline ◽  
Free Water ◽  
Tubular Reabsorption ◽  
Urine Flow ◽  
Constant Infusion ◽  
Threefold Increase ◽  
Anesthetized Dogs ◽  
Ice Water

The renal concentrating operation during hydropenia and during constant infusion of 2 m urea in isotonic saline was studied in 10 anesthetized dogs. PAH, exogenous creatinine and osmolal clearances were determined, as well as rates of Na and Cl excretion. Following two to four control periods body temperature was lowered to approximately 25°C by the use of an ice-water bath. The above measurements were then repeated during this steady state of hypothermia. PAH and creatinine clearances are reduced to approximately one-third of control values, while urine flow is not significantly changed. Thus, proportionately less filtered water is reabsorbed. Osmolal clearance is reduced, but this reduction is less than that of GFR so that a decrease in the tubular reabsorption of filtered osmotic particles occurs in hypothermia. This reduction in tubular reabsorption of solute is revealed further in a two to threefold increase in the percentage excretion of filtered NaCl and total osmotic substance. A greater decrease in the process which removes free water (TcHH2O) from the supposedly isotonic tubular fluid results in a reduction to one-third to one-fourth of the control values for TcHH2O. There would appear to be a dissociation of water and solute reabsorptions in hypothermia which indicates a decrease in the renal concentrating process.

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