Date of Award

Spring 1987

Document Type

Dissertation

Degree Name

Doctor of Engineering Science in Chemical Engineering

Department

Chemical Engineering, Chemistry and Environmental Science

First Advisor

Edward Charles Roche, Jr.

Second Advisor

Basil Baltzis

Third Advisor

Walter Nunez Duran

Fourth Advisor

David S. Kristol

Fifth Advisor

Arthur B. Ritter

Abstract

Movement of macromolecules across microvascular walls was studied in the hamster cheek pouch with intravital fluorescence microscopy. A graded series of Fluorescein Isothiocyanate labeled Dextrans(FITC) of 20,000 -70,000 molecular weight were used as representative macromolecular tracers. The time dependent extravasation of FITC-Dextrans was video taped for approximately two and a half hours. Permeation of macromolecules from individual microvessels was quantified by digital video image processing. Histograms of the light intensity distributions for selected fields at various times have been measured and used to construct integral optical density - time profiles of the extravasated fluorochromes for particular leaky sites. An integrated value of the Residence Time Distribution function of the tracer passing through the "pore" structure of a microvascular wall was obtained from experimental data. Linear velocities and dispersion coefficients were calculated by fitting the solution of a convection-diffusion equation with a step change in macromolecular concentration at the boundary. The Marquardt nonlinear regression algorithm was used to optimize parameters. The average linear velocities were 1.69 ± 0.54 x 10-7 cm/sec for FITC-Dx 20; 0.59 ± 0.17 x 10-7 cm/sec for FITC-Dx 40; and 0.45 ± 0.09 x 10-7 cm/sec for FITC-Dx 70. The effective dispersion coefficients decrease from 4.40 ± 1.45 x 10-12 cm2/sec for FITC-Dx 20 to 0.47 ± 0.09 x 10-12 cm-2/sec for FITC-Dx 40 and to 0.26 ± 0.07 x 10-12 cm-2/sec for FITC-Dx 70. These data suggest that convection is the predominant mode of transendothelial macromolecular transport in continuous subcutaneous microvessels and is an increasingly important mechanism as the molecular size of the molecules increases.

Postcapillary pressures were measured in a series of experiments using a servo-nulling system. These results were used to calculate the linear velocities and the dispersion coefficients using two models of restricted transport. It was shown that the Fiber-Matrix theory can be applied for the quantitative discription of the macromolecular transport.

In addition, the effect of UV-irradiation on the postcapillary pressure was investigated. The results indicate that pressure drops to about 25% of the control within 10 seconds of illumination. A possible mechanism for this phenomena is suggested.

Share

COinS