Placental transport function

1991 ◽  
Vol 3 (4) ◽  
pp. 345 ◽  
Author(s):  
H Schneider
Keyword(s):  
Blood Flow ◽  
Species Differences ◽  
Transport Function ◽  
Concentration Difference ◽  
Flow Rates ◽  
Placental Transport ◽  
Carrier Mediated Transport ◽  
Net Flux ◽  
Kinetics Of ◽  
Carrier Systems

Placental transport provides a means of supplying nutrients to and removing metabolites from the fetus. Transport is based on substrate exchange and net flux from mother to fetus or vice versa and can be a result of a concentration difference or of unidirectional carrier-mediated transport. Blood flow regulates delivery to and removal from the area of placental exchange, and rapidly crossing compounds are dependent on blood flow for their rate of passage. There are substantial species differences in terms of flow rates normalized for fetal weight and also in terms of vascular arrangement. The barrier can be overcome via paracellular water-filled channels or via a transcellular route. Hydrophilic molecules that are not actively transported diffuse through paracellular channels, and the placentae of rodents and primates are much more permeable than the placenta of the sheep. Many different substrates such as glucose, amino acids, electrolytes and vitamins are transported by carrier systems. Transport proteins are located in the microvillous and basal membranes of the trophoblast. Asymmetry in the kinetics of binding results in differences in influx and efflux at the interface with maternal and fetal blood, allowing directional net flux across the placenta. Immunoglobulins are believed to cross by receptor-mediated endocytosis.

The Effect of Altered Cerebral Blood Flow on the Cerebral Kinetics of Thiopental and Propofol in Sheep

2000 ◽  
Vol 93 (4) ◽  
pp. 1085-1094 ◽  
Author(s):  
Richard N. Upton ◽  
Guy L. Ludbrook ◽  
Cliff Grant ◽  
David J. Doolette
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Random Order ◽  
High Flow ◽  
Low Flow ◽  
Flow State ◽  
Concentration Difference ◽  
Blood Flows ◽  
Kinetics Of ◽  
The Brain

Background Thiopental and propofol are highly lipid-soluble, and their entry into the brain often is assumed to be limited by cerebral blood flow rather than by a diffusion barrier. However, there is little direct experimental evidence for this assumption. Methods The cerebral kinetics of thiopental and propofol were examined over a range of cerebral blood flows using five and six chronically instrumented sheep, respectively. Using anesthesia (2.0% halothane), three steady state levels of cerebral blood flow (low, medium, and high) were achieved in random order by altering arterial carbon dioxide tension. For each flow state, 250 mg thiopental or 100 mg propofol was infused intravenously over 2 min. To quantify cerebral kinetics, arterial and sagittal sinus blood was sampled rapidly for 20 min from the start of the infusion, and 1.5 h was allowed between consecutive infusions. Various models of cerebral kinetics were examined for their ability to account for the data. Results The mean baseline cerebral blood flows for the "high" flow state were over threefold greater than those for the low. For the high-flow state the normalized arteriovenous concentration difference across the brain was smaller than for the low-flow state, for both drugs. The data were better described by a model with partial membrane limitation than those with only flow limitation or dispersion. Conclusions The cerebral kinetics of thiopental and propofol after bolus injection were dependent on cerebral blood flow, despite partial diffusion limitation. Higher flows produce higher peak cerebral concentrations.

Evidence for the transport function of uricase, an oxidative enzyme

1987 ◽  
Vol 253 (4) ◽  
pp. F702-F711 ◽  
Author(s):  
W. T. Pordy ◽  
M. S. Lipkowitz ◽  
R. G. Abramson
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Anion Exchanger ◽  
Choline Chloride ◽  
Trans Position ◽  
Transport Function ◽  
Sodium Potassium ◽  
Pig Liver ◽  
Carrier Mediated Transport ◽  
Kinetics Of

[2-14C]urate uptake was examined in proteoliposomes prepared with phosphatidylcholine and either pig liver uricase or albumin, and in protein-free liposomes. Urate uptake was only evident in proteoliposomes that contained active uricase. Uptakes were indistinguishable in the presence and absence of inwardly directed gradients of sodium, potassium, or choline chloride or outwardly directed hydroxyl gradients. Both urate and allantoin accumulated within proteoliposomes during urate uptake; however, [2–14C]allantoin was not taken up by proteoliposomes. Urate uptake was accelerated in the presence of unlabeled urate in the trans position, saturable, and competitively inhibited by oxonate, findings consistent with carrier-mediated transport. Finally, the kinetics of urate uptake and oxidation were virtually identical, implying that the transporter is uricase. Thus, these studies provide evidence that uricase can function as a transport protein for urate when inserted in a lipid bilayer: transport via uricase is neither cation dependent (not a cotransporter) nor dependent on an exchangeable anion (not a urate/anion exchanger). Additionally, these studies demonstrate that neither urate nor allantoin cross lipid bilayers by simple or nonionic diffusion.

The Effect of Hematocrit on the Clearance of Small Molecules during Hemodialysis

1983 ◽  
Vol 6 (3) ◽  
pp. 127-130 ◽  
Author(s):  
C. Woffindin ◽  
N.A. Hoenich ◽  
D.N.S. Kerr
Keyword(s):  
Blood Flow ◽  
Regression Analysis ◽  
Small Molecules ◽  
Flat Plate ◽  
Flow Rate ◽  
Distribution Curve ◽  
Blood Flow Rate ◽  
Hollow Fibre ◽  
Urea Clearance ◽  
Flow Rates

Data collected during the evaluation of a series of hemodialysers were analysed to see the effect of hematocrit on the clearance of urea and creatinine. All evaluations were performed on patients with a range of hematocrits with a mean close to 20%. The urea clearance of those in the upper half of the distribution curve (mean hematocrit 29.4%) was not significantly different from that of patients in the lower half of the distribution curve (mean hematocrit 16.9%) whether the clearance was studied at high or low blood flow rates and with hollow fibre or flat plate disposable hemodialysers. Likewise, there was no correlation between hematocrit and urea clearance by regression analysis. In contrast, the clearance of creatinine was affected by hematocrit being greater at lower hematocrit values. This difference was independent of blood flow rate and dialyser type and was confirmed by regression analysis.

Derecruitment of filtration surface area in paraquat-injured isolated dog lungs

1990 ◽  
Vol 68 (4) ◽  
pp. 1581-1589 ◽  
Author(s):  
T. Shibamoto ◽  
J. C. Parker ◽  
A. E. Taylor ◽  
M. I. Townsley
Keyword(s):  
Blood Flow ◽  
Surface Area ◽  
Vascular Resistance ◽  
High Flow ◽  
Base Line ◽  
Flow Rates ◽  
Blood Flows ◽  
Capillary Filtration Coefficient ◽  
Specific Index ◽  
Filtration Surface

The capillary filtration coefficient (Kf,c) is a sensitive and specific index of vascular permeability if surface area remains constant, but derecruitment might affect Kf,c in severely damaged lungs with high vascular resistance. We studied the effect of high and low blood flow rates on Kf,c in papaverine-pretreated blood-perfused isolated dog lungs perfused under zone 3 conditions with and without paraquat (PQ, 10(-2) M). Three Kf,cs were measured successively at hourly intervals for 5 h. These progressed sequentially from isogravimetric blood flow with low vascular pressure (I/L) to high flow with low vascular pressure (H/L) to high flow with high vascular pressure (H/H). The blood flows of H/L and H/H were greater than or equal to 1.5 times that of I/L. There were no significant changes in Kf,c in lungs without paraquat over a 50-fold range of blood flow rates. At 3 h after PQ, I/L-Kf,c was significantly increased and both isogravimetric capillary pressure and total protein reflection coefficient were decreased from base line. At 4 and 5 h, H/L-Kf,c was significantly greater than the corresponding I/L-Kf,c (1.01 +/- 0.22 vs. 0.69 +/- 0.09 and 1.26 +/- 0.19 vs. 0.79 +/- 0.10 ml.min-1.cmH2O-1.100 g-1, respectively) and isogravimetric blood flow decreased to 32.0 and 12.0% of base line, respectively. Pulmonary vascular resistance increased to 12 times base line at 5 h after PQ. We conclude that Kf,c is independent of blood flow in uninjured lungs. However, Kf,c measured at isogravimetric blood flow underestimated the degree of increase in Kf,c in severely damaged and edematous lungs because of a high vascular resistance and derecruitment of filtering surface area.

Role of adenosine in postprandial and reactive hyperemia in canine jejunum

1992 ◽  
Vol 263 (4) ◽  
pp. G487-G493 ◽  
Author(s):  
D. R. Sawmiller ◽  
C. C. Chou
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Adenosine Deaminase ◽  
Reactive Hyperemia ◽  
Concentration Difference ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
Increased Blood Flow

The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum.

scholarly journals In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model

2021 ◽  
Vol 12 ◽  
Author(s):  
M G Vossen ◽  
S Pferschy ◽  
C Milacek ◽  
M Haidinger ◽  
Mario Karolyi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Protein Binding ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
Bovine Blood ◽  
Flow Rates ◽  
Dialysate Flow Rate

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.

Kinetics of V̇o2 and femoral artery blood flow during heavy-intensity, knee-extension exercise

2005 ◽  
Vol 99 (2) ◽  
pp. 683-690 ◽  
Author(s):  
Nicole D. Paterson ◽  
John M. Kowalchuk ◽  
Donald H. Paterson
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Time Course ◽  
Slow Component ◽  
Knee Extension ◽  
Artery Blood Flow ◽  
Phase 2 ◽  
Femoral Artery Blood Flow ◽  
Knee Extension Exercise ◽  
Kinetics Of

It has been suggested that, during heavy-intensity exercise, O2 delivery may limit oxygen uptake (V̇o2) kinetics; however, there are limited data regarding the relationship of blood flow and V̇o2 kinetics for heavy-intensity exercise. The purpose was to determine the exercise on-transient time course of femoral artery blood flow (Q̇leg) in relation to V̇o2 during heavy-intensity, single-leg, knee-extension exercise. Five young subjects performed five to eight repeats of heavy-intensity exercise with measures of breath-by-breath pulmonary V̇o2 and Doppler ultrasound femoral artery mean blood velocity and vessel diameter. The phase 2 time frame for V̇o2 and Q̇leg was isolated and fit with a monoexponent to characterize the amplitude and time course of the responses. Amplitude of the phase 3 response was also determined. The phase 2 time constant for V̇o2 of 29.0 s and time constant for Q̇leg of 24.5 s were not different. The change (Δ) in V̇o2 response to the end of phase 2 of 0.317 l/min was accompanied by a ΔQ̇leg of 2.35 l/min, giving a ΔQ̇leg-to-ΔV̇o2 ratio of 7.4. A slow-component V̇o2 of 0.098 l/min was accompanied by a further Q̇leg increase of 0.72 l/min (ΔQ̇leg-to-ΔV̇o2 ratio = 7.3). Thus the time course of Q̇leg was similar to that of muscle V̇o2 (as measured by the phase 2 V̇o2 kinetics), and throughout the on-transient the amplitude of the Q̇leg increase achieved (or exceeded) the Q̇leg-to-V̇o2 ratio steady-state relationship (ratio ∼4.9). Additionally, the V̇o2 slow component was accompanied by a relatively large rise in Q̇leg, with the increased O2 delivery meeting the increased V̇o2. Thus, in heavy-intensity, single-leg, knee-extension exercise, the amplitude and kinetics of blood flow to the exercising limb appear to be closely linked to the V̇o2 kinetics.

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