Potassium, sodium, water, and Donnan potential changes in the myofibrils of intact muscle fibres after exposure to ouabain and K-free Ringer

1988 ◽  
Vol 66 (8) ◽  
pp. 1057-1065
Author(s):  
C. N. Fong ◽  
J. A. M. Hinke
Keyword(s):  
Water Content ◽  
Compartment Model ◽  
Muscle Fibres ◽  
Donnan Potential ◽  
Two Compartment Model ◽  
Free Treatment ◽  
Intact Muscle ◽  
Frog Sartorius ◽  
Apparent Association Constants ◽  
Apparent Association

Frog sartorius muscles were superfused for 40 min with solutions of K-free Ringer, normal Ringer containing ouabain, or K-free Ringer containing ouabain. Changes in myoplasmic K and Na were measured with ion-selective microelectrodes; changes in total fibre K and Na were measured by means of atomic absorption spectroscopy; and changes in total fibre water content were obtained from wet and dry weights. Application of a two-compartment model permitted one to calculate (i) the K, Na, and water changes in the myofibrils and in the surrounding myoplasm (extramyofibrillar space); (ii) the changes in the transmyofibrillar Donnan potential (ED); and (iii) the changes in the ratio of the apparent association constants (kNa/kK) of the myofilament charge sites to Na and K. In the resting fibres, the K, Na, and water content of the myofibrils were calculated to be 82, 87, and 80% of total fibre content, respectively; ED was calculated as −4.5 mV; kNa/kK was calculated as 1.4. After a 40-min ouabain treatment, 12 mmol (per kg fibre water) of intrafibre K exchanged with 7.5 mmol of extrafibre Na, 6.4 mmol of myofibrillar K exchanged with an equal amount of extramyofibrillar Na, ED increased to −8.3 mV, and kNa/kK remained relatively constant. After a 40-min K-free treatment, the fibres gained 5.5 mmol of Na without any change in fibre K or water, the myofibrils shifted 9.3% of their water into the extramyofibrillar space instead of exchanging K for Na, ED increased to −10.7 mV, and kNa/kK decreased to 0.47. When ouabain and zero K were combined, an equimolar transmembrane K for Na exchange occurred, the myofibrils appeared to shift water and to exchange K for Na, ED increased to −14.3 mV, and kNa/kK decreased to 0.63. Analyses of other experiments involving Na-free superfusions suggest that the zero K-induced intrafibre water shift is dependent on an uncompensated net accumulation of Na in the extramyofibrillar myoplasm. These results indicate that the myofibrils in the intact fibre may adjust their water and electrolyte content quite differently during different perturbations, and that the myofibrillar changes need not mimic the whole fibre water and electrolyte changes.

Two-Compartment Model of Cholesterol Kinetics for Establishment of Treatment Strategy of LDL Apheresis in Nephrotic Hypercholesterolemia

1994 ◽  
Vol 12 (6) ◽  
pp. 317-326 ◽  
Author(s):  
Masatomo Yashiro ◽  
Eri Muso ◽  
Munehiro Matsushima ◽  
Ryoichi Nagura ◽  
Kenji Sawanishi ◽  
...  
Keyword(s):  
Treatment Strategy ◽  
Compartment Model ◽  
Ldl Apheresis ◽  
Two Compartment Model

Clearance and Non-Invasive Determination of the Hepatic Extraction of Indocyanine Green in Baboons and Man

1983 ◽  
Vol 64 (2) ◽  
pp. 207-212 ◽  
Author(s):  
S. L. Grainger ◽  
P. W. N. Keeling ◽  
I. M. H. Brown ◽  
J. H. Marigold ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Accurate Determination ◽  
Liver Blood Flow ◽  
Compartment Model ◽  
Hepatic Extraction ◽  
Non Invasive ◽  
Two Compartment Model ◽  
Hepatic Extraction Ratio ◽  
Plasma Disappearance Curve

1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and noninvasively after a single intravenous injection of ICG.

Studies on Water in Barnacle Muscle Fibres II. Role of ions and Organic Solutes in Swelling of Chemically-skinned Fibres

1981 ◽  
Vol 90 (1) ◽  
pp. 43-63
Author(s):  
M. E. CLARK ◽  
J. A. M. HINKE ◽  
M. E. TODD
Keyword(s):  
Water Content ◽  
Fibre Volume ◽  
Tween 20 ◽  
Muscle Fibres ◽  
Skinned Fibres ◽  
Organic Solutes ◽  
Net Charge ◽  
Trimethylamine Oxide ◽  
Organic Solute

Single muscle fibres from the giant barnacle, Balanus nubilis, were chemically skinned (2% Tween 20), then equilibrated for 40 h in salt solutions ranging in ionic strength from 0·025 to 0·6M at pH 7·0. The water content of the fibres and the net charge on the myofilaments increased with increasing salt concentration. Cation accumulation in the fibres was about equal to anion exclusion at all salt concentrations. When an organic solute (trimethylamine oxide, glycine, alanine, serine, proline, or glycerol) in the concentration range from 0·1 to 0·6 M was added to the salt solution, cation accumulation increased and water content decreased. Myofilament architecture was disrupted when the fibres were equilibrated in high salt (> 0·4 M) solutions and preserved when 0·5 M-triethylamine oxide was also added. The results are consistent with the view that organic solutes enhance the association between the fixed charge sites and their counterions. This hypothesis is examined quantitatively using the Oosawa relationship between the volume and the counterion association for cylindrical polyelectrolytes. The results illustrate that organic solutes can influence fibre volume in a way other than through osmo-regulation.

scholarly journals Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin.

1996 ◽  
Vol 40 (1) ◽  
pp. 105-109 ◽  
Author(s):  
M Dreetz ◽  
J Hamacher ◽  
J Eller ◽  
K Borner ◽  
P Koeppe ◽  
...  
Keyword(s):  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Dose Administration ◽  
Microdilution Method ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Renal Clearances ◽  
The Mean ◽  
Bactericidal Activities

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.

scholarly journals A comparison of the short-term kinetics of zinc metabolism in women during fasting and following a breakfast meal

1998 ◽  
Vol 80 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Nicola M. Lowe ◽  
Leslie R. Woodhouse ◽  
Janet C. King
Keyword(s):  
Energy Content ◽  
Compartment Model ◽  
Zinc Metabolism ◽  
Short Term ◽  
Compartment System ◽  
Breakfast Meal ◽  
Physiological Importance ◽  
Two Compartment Model ◽  
Zn Concentration ◽  
Kinetics Of

The physiological importance and mechanism of the postprandial fall in plasma Zn concentration is not well understood. In order to gain further information on this apparent redistribution of plasma Zn, a stable isotope, 70Zn, was used to study the effect of a breakfast meal on plasma Zn kinetics. Nine women participated in two trials, a fasting trial and a breakfast-meal trial; five of the women participated in a third trial in which the energy content of the breakfast meal was doubled. At each trial, 0.1mg of 70Zn was infused intravenously, and the plasma disappearance of the isotope was analysed using a two-compartment model of Zn kinetics. Plasma Zn concentration fell significantly following the two trials in which the subjects were given meals, reaching low points that were 13 and 19 %, respectively, below concentrations at comparable times during the fasting trial. Kinetic analysis revealed that after the doubled breakfast meal there was a significant fall (P < 0.007) in the size of the most rapidly turning over Zn pool (pool (a)) from 2.90 (se 0.13)mg in the fasting state to 2.47 (se 0.14) mg postprandially. The fractional turnover rate of pool (a) to other extravascular Zn pools, i.e. outside the two-compartment system, was also significantly elevated after the doubled breakfast meal (P < 0.05). These results suggest that the decline in plasma Zn concentration following a meal is due to a redistribution of Zn from the plasma to other more slowly turning over extravascular pools that may be involved in the assimilation and metabolism of fuels following food intake.

scholarly journals Population Pharmacokinetic Analysis of Voriconazole and Anidulafungin in Adult Patients with Invasive Aspergillosis

2014 ◽  
Vol 58 (8) ◽  
pp. 4718-4726 ◽  
Author(s):  
Ping Liu ◽  
Diane R. Mould
Keyword(s):  
Invasive Aspergillosis ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Institutional Review Boards ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
First Order ◽  
Two Compartment Model

ABSTRACTTo assess the pharmacokinetics (PK) of voriconazole and anidulafungin in patients with invasive aspergillosis (IA) in comparison with other populations, sparse PK data were obtained for 305 adults from a prospective phase 3 study comparing voriconazole and anidulafungin in combination versus voriconazole monotherapy (voriconazole, 6 mg/kg intravenously [IV] every 12 h [q12h] for 24 h followed by 4 mg/kg IV q12h, switched to 300 mg orally q12h as appropriate; with placebo or anidulafungin IV, a 200-mg loading dose followed by 100 mg q24h). Voriconazole PK was described by a two-compartment model with first-order absorption and mixed linear and time-dependent nonlinear (Michaelis-Menten) elimination; anidulafungin PK was described by a two-compartment model with first-order elimination. For voriconazole, the normal inverse Wishart prior approach was implemented to stabilize the model. Compared to previous models, no new covariates were identified for voriconazole or anidulafungin. PK parameter estimates of voriconazole and anidulafungin are in agreement with those reported previously except for voriconazole clearance (the nonlinear clearance component became minimal). At a 4-mg/kg IV dose, voriconazole exposure tended to increase slightly as age, weight, or body mass index increased, but the difference was not considered clinically relevant. Estimated voriconazole exposures in IA patients at 4 mg/kg IV were higher than those reported for healthy adults (e.g., the average area under the curve over a 12-hour dosing interval [AUC0–12] at steady state was 46% higher); while it is not definitive, age and concomitant medications may impact this difference. Estimated anidulafungin exposures in IA patients were comparable to those reported for the general patient population. This study was approved by the appropriate institutional review boards or ethics committees and registered on ClinicalTrials.gov (NCT00531479).

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