Pyroelectric Catalysis-Based “Nano-Lymphatic” Reduces Tumor Interstitial Pressure for Enhanced Penetration and Hydrodynamic Therapy

In order to understand how interstitial fluid pressure and flow affect cell behavior, many studies use microfluidic approaches to apply externally controlled pressures to the boundary of a cell-containing gel. It is generally assumed that the resulting interstitial pressure distribution quickly reaches a steady-state, but this assumption has not been rigorously tested. Here, we demonstrate experimentally and computationally that the interstitial fluid pressure within an extracellular matrix gel in a microfluidic device can, in some cases, react with a long time delay to external loading. Remarkably, the source of this delay is the slight (∼100 nm in the cases examined here) distension of the walls of the device under pressure. Finite-element models show that the dynamics of interstitial pressure can be described as an instantaneous jump, followed by axial and transverse diffusion, until the steady pressure distribution is reached. The dynamics follow scaling laws that enable estimation of a gel's poroelastic constants from time-resolved measurements of interstitial fluid pressure.

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Resistance of Tumor Interstitial Pressure to the Penetration of Intraperitoneally Delivered Antibodies into Metastatic Ovarian Tumors

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-04-2332 ◽

2005 ◽

Vol 11 (8) ◽

pp. 3117-3125 ◽

Cited By ~ 59

Author(s):

Michael F. Flessner ◽

Jaewah Choi ◽

Kimberly Credit ◽

Ravi Deverkadra ◽

Karla Henderson

Keyword(s):

Ovarian Tumors ◽

Interstitial Pressure

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Computational modeling of PET tracer distribution in solid tumors integrating microvasculature

BMC Biotechnology ◽

10.1186/s12896-021-00725-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Niloofar Fasaeiyan ◽

M. Soltani ◽

Farshad Moradi Kashkooli ◽

Erfan Taatizadeh ◽

Arman Rahmim

Keyword(s):

Blood Flow ◽

Computational Modeling ◽

Interstitial Fluid ◽

Diffusion Reaction ◽

Surrounding Tissue ◽

Tissue Type ◽

Computational Domain ◽

Interstitial Pressure ◽

Coupled Modeling ◽

Tumor Region

Abstract Background We present computational modeling of positron emission tomography radiotracer uptake with consideration of blood flow and interstitial fluid flow, performing spatiotemporally-coupled modeling of uptake and integrating the microvasculature. In our mathematical modeling, the uptake of fluorodeoxyglucose F-18 (FDG) was simulated based on the Convection–Diffusion–Reaction equation given its high accuracy and reliability in modeling of transport phenomena. In the proposed model, blood flow and interstitial flow are solved simultaneously to calculate interstitial pressure and velocity distribution inside cancer and normal tissues. As a result, the spatiotemporal distribution of the FDG tracer is calculated based on velocity and pressure distributions in both kinds of tissues. Results Interstitial pressure has maximum value in the tumor region compared to surrounding tissue. In addition, interstitial fluid velocity is extremely low in the entire computational domain indicating that convection can be neglected without effecting results noticeably. Furthermore, our results illustrate that the total concentration of FDG in the tumor region is an order of magnitude larger than in surrounding normal tissue, due to lack of functional lymphatic drainage system and also highly-permeable microvessels in tumors. The magnitude of the free tracer and metabolized (phosphorylated) radiotracer concentrations followed very different trends over the entire time period, regardless of tissue type (tumor vs. normal). Conclusion Our spatiotemporally-coupled modeling provides helpful tools towards improved understanding and quantification of in vivo preclinical and clinical studies.

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Soft-Tissue Sarcoma: A Cause of Increased Interstitial Pressure

Orthopedics ◽

10.3928/0147-7447-20031101-18 ◽

2003 ◽

Vol 26 (11) ◽

pp. 1151-1152

Author(s):

Richard L McGough ◽

Paul D Fadale ◽

Richard M Terek

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Interstitial Pressure

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Renal interstitial pressure in mineralocorticoid escape

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.3.f396 ◽

1985 ◽

Vol 249 (3) ◽

pp. F396-F399 ◽

Cited By ~ 2

Author(s):

J. C. Burnett ◽

J. A. Haas ◽

M. S. Larson

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Hydrostatic Pressure ◽

Arterial Pressure ◽

Filtration Rate ◽

Interstitial Pressure ◽

Peritubular Capillary ◽

Renal Interstitium ◽

Vasa Recta ◽

Peritubular Capillaries

Studies were performed in normal and DOCA-treated rats to determine renal hydrostatic pressures within superficial peritubular capillaries, the vasa recta, and renal interstitium during mineralocorticoid escape to test the hypothesis that mineralocorticoid escape is associated with elevated renal interstitial hydrostatic pressure. Fractional sodium excretion was greater in the DOCA-treated rats (3.20 +/- 0.51%) compared with control rats (1.23 +/- 0.12%) with no difference in glomerular filtration rate and renal blood flow between the two groups. Superficial peritubular capillary hydrostatic pressure (13.4 +/- 0.6 vs. 8.3 +/- 0.3 mmHg), vasa recta hydrostatic pressure (13.8 +/- 0.5 vs. 9.0 +/- 0.4 mmHg), renal interstitial hydrostatic pressure (9.8 +/- 0.4 vs. 4.5 +/- 0.4 mmHg), and arterial pressure (145 +/- 6 vs. 120 +/- 7 mmHg) were greater in the DOCA-treated compared with the control rats. These studies establish that mineralocorticoid escape is characterized by high renal interstitial hydrostatic pressure.

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Gravity-dependent distribution of parietal subpleural interstitial pressure

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.5.1912 ◽

1987 ◽

Vol 63 (5) ◽

pp. 1912-1918 ◽

Cited By ~ 9

Author(s):

D. Negrini ◽

C. Capelli ◽

M. Morini ◽

G. Miserocchi

Keyword(s):

Parietal Pleura ◽

Hydraulic Pressure ◽

Interstitial Pressure ◽

Liquid Pressure ◽

Exposed Area ◽

Muscular Layer ◽

Simultaneous Measurements ◽

Pleural Surface ◽

Tidal Change ◽

Spontaneously Breathing

Using liquid-filled catheters, we recorded, in 30 anesthetized, spontaneously breathing supine rabbits, the hydraulic pressure from the parietal subpleural interstitial space (Pspl). Through a small exposed area of parietal pleura a plastic catheter (1 mm ED), with a closed and smooth tip and several holes on the last centimeter, was carefully advanced between the muscular layer and the parietal pleura, tangentially to the pleural surface to reach the submesothelial layer. Simultaneous measurements of pleural liquid pressure (Pliq) were obtained from intrapleurally placed cannulas. End-expiratory Pspl decreased (became more negative) with increasing height (LH) according to the following: Pspl (cmH2O) = -1 - 0.4 LH (cm), the corresponding equation for Pliq being Pliq (cmH2O) = -1.5 – 0.7 LH (cm). Thus at end expiration a transpleural hydraulic pressure difference (Pliq-Pspl) developed at any height, increasing from the bottom to the top of the cavity as Pliq - Pspl (cmH2O) = -0.5 – 0.3 LH (cm). The Pliq-Pspl difference increased during inspiration due to the much smaller tidal change in Pspl than in Pliq. By considering the gravity-dependent distribution of the functional hydrostatic pressure in the systemic capillaries of the pleura (Pc) and the Pspl and Pliq values integrated over the respiratory cycle we estimated that on the average, the Pc-Pspl difference is sevenfold larger than the Pspl-Pliq difference.

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Effect of vascular pressure on interstitial pressures in the isolated dog lung

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.1.268 ◽

1993 ◽

Vol 75 (1) ◽

pp. 268-272 ◽

Cited By ~ 7

Author(s):

M. R. Glucksberg ◽

J. Bhattacharya

Keyword(s):

Pressure Gradient ◽

Airway Pressure ◽

Pleural Pressure ◽

Interstitial Pressure ◽

Direct Measurements ◽

Intravascular Pressure

We report the first direct measurements of the effect of pulmonary vascular pressures on perialveolar interstitial pressures. In seven experiments we varied the intravascular pressure (Pvas) in isolated dog lungs held at constant airway pressure (PA). By the micropuncture servo-null technique, we recorded perialveolar interstitial pressures with respect to pleural pressure (0 cmH2O) at the alveolar junctions (Pjct) and in microvascular adventitia (Padv). At PA = 7 cmH2O, increase from 5 to 15 cmH2O did not affect Pjct, although it decreased Padv by 1.2 +/- 0.4 cmH2O. The Pjct-Padv gradient increased by 77%. Increasing Pvas to 25 cmH2O had no further effect on either interstitial pressure. In four experiments we also determined interstitial pressure in the hilum (Phil). When Pvas was increased from 5 to 15 cmH2O, Phil increased by 4.5 +/- 0.9 cmH2O. Further elevation of Pvas to 25 cmH2O increased Phil further by 2.4 +/- 0.4 cmH2O. At PA = 15 cmH2O, all interstitial pressures decreased, but their responses to Pvas were similar. We conclude that increase of Pvas 1) increases Phil but not perialveolar interstitial pressures and 2) increases the perialveolar interstitial pressure gradient, which may promote local liquid clearance.

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