Intrinsic pump-conduit behavior of lymphangions

2007 ◽  
Vol 292 (4) ◽  
pp. R1510-R1518 ◽  
Author(s):  
Christopher M. Quick ◽  
Arun M. Venugopal ◽  
Anatoliy A. Gashev ◽  
David C. Zawieja ◽  
Randolph H. Stewart

Lymphangions, segments of lymphatic vessels bounded by valves, have characteristics of both ventricles and arteries. They can act primarily like pumps when actively transporting lymph against a pressure gradient. They also can act as conduit vessels when passively transporting lymph down a pressure gradient. This duality has implications for clinical treatment of several types of edema, since the strategy to optimize lymph flow may depend on whether it is most beneficial for lymphangions to act as pumps or conduits. To address this duality, we employed a simple computational model of a contracting lymphangion, predicted the flows at both positive and negative axial pressure gradients, and validated the results with in vitro experiments on bovine mesenteric vessels. This model illustrates that contraction increases flow for normal axial pressure gradients. With edema, limb elevation, or external compression, however, the pressure gradient might reverse, and lymph may flow passively down a pressure gradient. In such cases, the valves may be forced open during the entire contraction cycle. The vessel thus acts as a conduit, and contraction has the effect of increasing resistance to passive flow, thus inhibiting flow rather than promoting it. This analysis may explain a possible physiological benefit of the observed flow-mediated inhibition of the lymphatic pump at high flow rates.

2009 ◽  
Vol 296 (3) ◽  
pp. H662-H668 ◽  
Author(s):  
Christopher M. Quick ◽  
Bruce L. Ngo ◽  
Arun M. Venugopal ◽  
Randolph H. Stewart

Lymphangions, the segments of lymphatic vessels between valves, exhibit structural characteristics in common with both ventricles and arteries. Although once viewed as passive conduits like arteries, it has become well established that lymphangions can actively pump lymph against an axial pressure gradient from low-pressure tissues to the great veins of the neck. A recently reported mathematical model, based on fundamental principles, predicted that lymphangions can transition from pump to conduit behavior when outlet pressure falls below inlet pressure. In this case, the axial pressure gradient becomes the major source of energy for the propulsion of lymph, despite the presence of cyclical contraction. In fact, flow is augmented when cyclical contractions are abolished. We therefore used an in vitro preparation to confirm these findings and to test the hypothesis that lymphangion contraction inhibits flow when outlet pressure falls below inlet pressure. Bovine postnodal mesenteric lymphatic vessels harvested from an abattoir were subjected to an inlet pressure of 5.0 cmH2O and an outlet pressure that decreased from 6.5 to 3.5 cmH2O under control conditions, stimulated with U-46619 (a thromboxane analog) and relaxed with calcium-free solution. Under control conditions, lymphatic flow markedly increased as outlet pressure fell below inlet pressure. In this case, the slopes of the flow versus axial pressure gradient increased with calcium-free conditions (61%, n = 8, P = 0.016) and decreased with U-46619 stimulation (21%, n = 5, P = 0.033). Our findings indicate that the stimulation of lymphatic contractility does indeed inhibit lymphatic flow when vessels act like conduits.


2013 ◽  
Vol 135 (9) ◽  
Author(s):  
Tarrah A. Herrmann ◽  
Andrew W. Siefert ◽  
Gregg S. Pressman ◽  
Hannah R. Gollin ◽  
Steven A. Touchton ◽  
...  

Mitral annular calcification (MAC) involves calcium deposition in the fibrous annulus supporting the mitral valve (MV). When calcification extends onto the leaflets, valve opening can be restricted. The influence of MAC MV geometry on Doppler gradients is unknown. This study describes a novel methodology to rapid-prototype subject-specific MAC MVs. Replicated valves were used to assess the effects of distorted annular-leaflet geometry on Doppler-derived, transmitral gradients in comparison to direct pressure measurements and to determine if transmitral gradients vary according to measurement location. Three-dimensional echocardiography data sets were selected for two MAC MVs and one healthy MV. These MVs were segmented and rapid prototyped in their middiastolic configuration for in vitro testing. The effects of MV geometry, measurement modality, and measurement location on transmitral pressure gradient were assessed by Doppler and catheter at three locations along the MV's intercommissural axis. When comparing dimensions of the rapid-prototyped valves to the subject echocardiography data sets, mean relative errors ranged from 6.2% to 35%. For the evaluated MVs, Doppler pressure gradients exhibited good agreement with catheter-measured gradients at a variety of flow rates, though with slight systematic overestimation in the recreated MAC valves. For all of the tested MVs, measuring the transmitral pressure gradient at differing valve orifice positions had minimal impact on observed gradients. Upon the testing of additional normal and calcific MVs, these data may contribute to an improved clinical understanding of MAC-related mitral stenosis. Moreover, they provide the ability to statistically evaluate between measurement locations, flow rates, and valve geometries for Doppler-derived pressure gradients. Determining these end points will contribute to greater clinical understanding for the diagnosis MAC patients and understanding the use and application of Doppler echocardiography to estimate transmitral pressure gradients.


1996 ◽  
Vol 270 (2) ◽  
pp. R486-R488 ◽  
Author(s):  
R. E. Drake ◽  
S. Dhother ◽  
V. M. Oppenlander ◽  
J. C. Gabel

We determined the relationship between flow rate and inflow pressure for intestinal lymphatic vessels in six sheep. First we anesthetized the sheep and cannulated both ends of a 6- to 10-cm-long segment of intestinal lymphatic. We allowed the sheep to recover from the anesthesia for 2-24 h. To determine the flow rate-inflow pressure relationship, we recorded the inflow pressure and infused Ringer solution into the lymphatic at rates from 34 to 510 microliters/min. The flow rate-pressure relationship was not linear and it had two regions. For flow rates less than approximately 150 microliters/min, inflow pressure was greater than outflow pressure. Thus the lymphatic pumped fluid against a pressure gradient. For flow rates > 150 microliters/min, inflow pressure was greater than outflow pressure, and we attributed most of the flow to the favorable inflow-outflow pressure gradient (passive flow). When we used verapamil to inhibit lymphatic pumping, we found no flow for inflow pressure less than outflow pressure, and flow increased linearly for inflow pressure greater than outflow pressure. Our data for actively pumping lymphatic vessels are consistent with the flow vs. pressure relationships derived from mathematical models of the lymphatic pump. Furthermore, our data with verapamil confirm that active lymphatic pumping was responsible for the nonlinear flow vs. pressure relationship for the lymphatic vessels.


2011 ◽  
Vol 301 (1) ◽  
pp. H48-H60 ◽  
Author(s):  
Michael J. Davis ◽  
Elaheh Rahbar ◽  
Anatoliy A. Gashev ◽  
David C. Zawieja ◽  
James E. Moore

Secondary lymphatic valves are essential for minimizing backflow of lymph and are presumed to gate passively according to the instantaneous trans-valve pressure gradient. We hypothesized that valve gating is also modulated by vessel distention, which could alter leaflet stiffness and coaptation. To test this hypothesis, we devised protocols to measure the small pressure gradients required to open or close lymphatic valves and determine if the gradients varied as a function of vessel diameter. Lymphatic vessels were isolated from rat mesentery, cannulated, and pressurized using a servo-control system. Detection of valve leaflet position simultaneously with diameter and intraluminal pressure changes in two-valve segments revealed the detailed temporal relationships between these parameters during the lymphatic contraction cycle. The timing of valve movements was similar to that of cardiac valves, but only when lymphatic vessel afterload was elevated. The pressure gradients required to open or close a valve were determined in one-valve segments during slow, ramp-wise pressure elevation, either from the input or output side of the valve. Tests were conducted over a wide range of baseline pressures (and thus diameters) in passive vessels as well as in vessels with two levels of imposed tone. Surprisingly, the pressure gradient required for valve closure varied >20-fold (0.1–2.2 cmH2O) as a passive vessel progressively distended. Similarly, the pressure gradient required for valve opening varied sixfold with vessel distention. Finally, our functional evidence supports the concept that lymphatic muscle tone exerts an indirect effect on valve gating.


2021 ◽  
Author(s):  
Nikolay Baryshnikov ◽  
Evgeniy Zenchenko ◽  
Sergey Turuntaev

<p>Currently, a number of studies showing that the injection of fluid into the formation can cause induced seismicity. Usually, it is associated with a change in the stress-strain state of the reservoir during the pore pressure front propagation. Modeling this process requires knowledge of the features of the filtration properties of reservoir rocks. Many researchers note the fact that the measured permeability of rock samples decreases at low pressure gradients. Among other things, this may be due to the formation of boundary adhesion layers with altered properties at the interfaces between the liquid and solid phases. The characteristic thickness of such layer can be fractions of a micron, and the effect becomes significant when filtering the fluid in rocks with a comparable characteristic pore size. The purpose of this work was to study the filtration properties of rock samples with low permeability at low flow rates. Laboratory modeling of such processes is associated with significant technical difficulties, primarily with the accuracy limit of measuring instruments when approaching zero speed values. The technique used by us to conduct the experiment and data processing allows us to study the dependence of the apparent permeability on the pore pressure gradient in the range of 0.01 MPa/m, which is comparable to the characteristic pressure gradients during the development of oil fields. In the course of the study, we carried out laboratory experiments on limestone core samples, during which the dependencies of their apparent permeability on the pore pressure gradient were obtained. We observed a significant decrease in their permeability at low flow rates. In the course of analyzing the experimental results, we proposed that a decrease in apparent permeability may occur due to the effect of even a small amount of residual gas in the pore space of the samples. This has been confirmed by additional experiments. The possibility of clogging of core sample pore space must be considered when conducting when conducting laboratory studies of the core apparent permeability.</p>


Perfusion ◽  
2002 ◽  
Vol 17 (2) ◽  
pp. 153-156 ◽  
Author(s):  
Anja Gerdes ◽  
Thorsten Hanke ◽  
Hans-H Sievers

Background: Prevention of intraoperative plaque dislodgement in patients with atherosclerotic ascending aorta by development of innovative aortic cannula designs gains growing interest in cardiac surgery. To increase knowledge about the hydrodynamics of the innovative Embol-X™ cannula, which includes an intra-aortic filter device targeting at atheromatous emboli capture, was the aim of the present study. Methods: Pressure gradients and back pressures of the Embol-X™ cannula were measured at varying flow rates in a mock circulation and compared with two commonly used single-stream cannulae. Results: At a flow rate of 5.5 l/min, pressure gradients across the Argyle™ and the RMI cannulae were 48% and 62% and back pressures 25% and 47% lower than the corresponding values across the Embol-X™ cannula. Conclusions: The novel concept of integrating a filter device may provide clinical advantages concerning neurologic outcome. Further in vivo studies seem to be desirable to obtain more information concerning the clinical effects of the Embol-X™ cannula hydrodynamics.


1993 ◽  
Vol 265 (1) ◽  
pp. R97-R102 ◽  
Author(s):  
J. Eisenhoffer ◽  
R. M. Elias ◽  
M. G. Johnston

The objective of this study was to determine how lymphatic vessels responded to outflow pressure changes in vitro. Bovine mesenteric lymphatics were suspended in an organ bath preparation with both inflow and outflow ends cannulated. Input to the duct was provided from a reservoir filled with Krebs solution. To initiate pumping, a transmural pressure was applied to the ducts by elevating the fluid reservoir and outflow catheters and making their heights equal to one another. The outflow catheter was then elevated above the liquid in the reservoir in 2-cmH2O increments, and pumping activity was monitored for 10 min at each outflow pressure. Outflow pressures were calculated as the product of the flow rate and outflow cannula resistance plus the height of the tip of the outflow catheter above the liquid in the organ bath. At low transmural pressures (2-4 cmH2O), elevations in outflow pressure often had little effect on flow rates until high outflow pressures had been attained. In contrast, elevations in outflow pressures resulted in an increasingly rapid decline in flow rates as transmural pressures were incrementally increased. The mean power (in mu W) required to produce the observed flow rate was estimated at each outflow pressure as the product of the flow rate and the pressure across the lymphatic vessel. The ability of the lymphatics to generate sustained or enhanced power output in response to an increasing outflow pressure challenge was most pronounced at lower transmural pressures. As transmural pressures were increased, the range of outflow pressures that stimulated increased power production was diminished. We conclude that elevations in outflow pressure in an in vitro preparation result in a nonlinear decline in flow rates. This nonlinearity is due to an active lymphatic pump mechanism.


1963 ◽  
Vol 3 (01) ◽  
pp. 59-69 ◽  
Author(s):  
George H. Fancher ◽  
Kermit E. Brown

Abstract An 8,000-ft experimental field well was utilized to conduct flowing pressure gradient tests under conditions of continuous, multiphase flow through 2 3/8-in. OD tubing. The well was equipped with 10 gas-lift valves and 10 Maihak electronic pressure recorders, as well as instruments to accurately measure the surface pressure, temperature, volume of injected gas and fluid production.These tests were conducted for flow rates ranging from 75 to 936 B/D at various gas-liquid ratios from 105 to 9,433 scf/bbl. An expanding-orifice gas-lift valve allowed each flow rate to be produced with a range of controlled gas-liquid ratios. From these data an accurate pressure traverse has been constructed for various flow rates and for various gas-liquid ratios.A comparison of these tests to Poettmann and Carp enter's correlation indicates that deviations occur for certain ranges of flow rates and gasliquid ratios. Numerous curves are presented illustrating the comparison of this correlation with the field data. Poettmann and Carpenter's correlation deviates some for low flow rates and, in particular, for gas-liquid ratios in excess of 3,000 scf/bbl. These deviations are believed to be mainly due to the friction-factor correlation. However, Poettmann and Carpenter's correlation gives excellent agreement in those ranges of higher density. This was as expected and predicted by Poettmann. He pointed out that their method was not intended to be extended to those ranges of low densities whereby an extreme reversal in curvature occurs.As a result of these experimental tests, correlations using Poettmann and Carpenter's method were established between the friction factors and mass flow rates which are applicable for all gasliquid ratios and flow rates. Definite changing flow patterns do not allow any one correlation to be accurate for all ranges of flow. Introduction The ability to analytically predict the pressure at any point in a flow string is essential in determining optimum production string dimensions and in the design of gas-lift installations. This information is also invaluable in predicting bottom-hole pressures in flowing wells.Although this problem is not new to industry, it has by no means been solved completely for all types of flow conditions. Versluys, Uren, et al, Gosline, May, and Moore, et al, were all early investigators of multiphase flow through vertical conduits. However, all of these investigations and proposed methods were very limited as to their range of application. Likewise, many are extremely complicated and therefore not very useful in the field.Only in the last decade have any significant methods been proposed which are generally applicable. The most widely accepted procedure in industry at the present time is a semi-empirical method developed from an energy balance, proposed by Poettmann and Carpenter in 1952. Their correlation is based on actual pressure measurements from field wells. Accurate predictions from this correlation are limited to high flow rates and low gas-liquid ratios.Although this method will he discussed in detail later, it should be pointed out that two important parameters, namely the gas-liquid ratio and the viscosity, were omitted in their correlation. The viscosity was justifiably omitted since their data was in the highly turbulent flow region for both phases, and most wells fall in this category. The gas-liquid ratio was incorporated to some extent in the gas-density term. In 1954, Gilbert presented numerous pressure gradient curves obtained from field data for various flow rates and gas-liquid ratios for the determination of optimum flow strings. However, no method is presented for predicting pressure gradients except by comparison to these curves. SPEJ P. 59^


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lauren Andrews ◽  
Scott Benken ◽  
Xing Tan ◽  
Eric Wenzler

Abstract Background To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods Apixaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for apixaban were estimated via noncompartmental analysis. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was utilized to provide dosing estimations for flow rates from 0.5–5 L/h. Results Mean adsorption to the HF1400 and M150 filters differed significantly at 38 and 13%, respectively, while mean (± standard deviation, SD) percent protein binding was 70.81 ± 0.01%. Effect of CVVH point of dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 2.5–7.5 mg twice daily (BID) may be needed for flow rates ranging from 0.5–5 L/h, respectively. Conclusion For CRRT flow rates most commonly employed in clinical practice, the standard labeled 5 mg BID dose of apixaban is predicted to achieve target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.


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