Dynamics of Transcapillary Fluid Exchange

Fluid balance at the capillary level has been simulated with an analogue computer program, based on experimental data on regional differences in capillary permeability, surface areas, and hydrostatic pressures. The program takes into account fluid and protein fluxes into and out of the interstitial space. Solutions are obtained for tissue hydrostatic pressure, tissue fluid osmotic pressure, interstitial space volume, and lymph flow. Simulation of a variety of physiological experiments and clinical disease states has yielded reasonable agreement between experimental data and data obtained by computer analysis. Dilution of the interstitial plasma protein pool with a consequent reduc6tion of its oncotic pressure appears to be a major factor, which prevents edema unless plasma oncotic pressures are reduced by 10–15 mm Hg or, alternatively, venous pressures are elevated by a similar amount. The computer analysis in all instances yields positive values for tissue pressure, in agreement with experimental data obtained by needle puncture. The negative tissue pressures observed in subcutaneous capsules can be reproduced in the computer program, if the interface between the capsule and the surrounding interstitial space is assumed to have the properties of a semipermeable membrane

Peristaltic Pumping of Blood Through Small Vessels of Varying Cross-section

The paper is devoted to a study of the peristaltic motion of blood in the micro-circulatory system. The vessel is considered to be of varying cross-section. The progressive peristaltic waves are taken to be of sinusoidal nature. Blood is considered to be a Herschel-Bulkley fluid. Of particular concern here is to investigate the effects of amplitude ratio, mean pressure gradient, yield stress and the power law index on the velocity distribution, streamline pattern and wall shear stress. On the basis of the derived analytical expression, extensive numerical calculations have been made. The study reveals that velocity of blood and wall shear stress are appreciably affected due to the non-uniform geometry of blood vessels. They are also highly sensitive to the magnitude of the amplitude ratio and the value of the fluid index.Comment: Accepted for publication in ASME journal of Applied Mechanics. arXiv admin note: text overlap with arXiv:1108.1285v

Non-Newtonian characteristics of peristaltic flow of blood in micro-vessels

Of concern in the paper is a generalized theoretical study of the non-Newtonian characteristics of peristaltic flow of blood through micro-vessels, e.g. arterioles. The vessel is considered to be of variable cross-section and blood to be a Herschel-Bulkley type of fluid. The progressive wave front of the peristaltic flow is supposed sinusoidal/straight section dominated (SSD) (expansion/contraction type); Reynolds number is considered to be small with reference to blood flow in the micro-circulatory system. The equations that govern the non-Newtonian peristaltic flow of blood are considered to be non-linear. The objective of the study has been to examine the effect of amplitude ratio, mean pressure gradient, yield stress and the power law index on the velocity distribution, wall shear stress, streamline pattern and trapping. It is observed that the numerical estimates for the aforesaid quantities in the case of peristaltic transport of the blood in a channel are much different from those for flow in an axisymmetric vessel of circular cross-section. The study further shows that peristaltic pumping, flow velocity and wall shear stress are significantly altered due to the non-uniformity of the cross-sectional radius of blood vessels of the micro-circulatory system. Moreover, the magnitude of the amplitude ratio and the value of the fluid index are important parameters that affect the flow behaviour. Novel features of SSD wave propagation that affect the flow behaviour of blood have also been discussed.Comment: Accepted for publication in Communications in Nonlinear Science and Numerical Simulation, Elsevier. arXiv admin note: text overlap with arXiv:1006.017

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome