Physical models of vascular systems are being used extensively in our laboratory to study a variety of hemodynamic phenomena. During the past year, the major effort has been directed to projects in the following two categories: (1) hemodynamic studies related to flow in coronary arteries; and (2) intracarotid infusions of methotrexate following blood-brain barrier disruption with hypertonic mannitol. (1) The onset of turbulence during oscillating flow has been studied in a series of straight, rigid tubes. An empirical correlation was developed that would predict the transition from laminar to turbulent flow as a function of the peak flow (Reynolds number), the frequency of oscillation (Womersley parameter), and the stroke volume (Strouhal number). Similar experiments were performed with branched tubes of two different area ratios, and in models of pig coronaries. Turbulence correlations were also derived for these configurations. (2) Blood-brain barrier disruption (BBBD) was conducted on human subjects with malignant brain tumors using thirty second infusions of hypertonic mannitol. The disruption, designed to increase drug permeability in the tumor, was immediately followed by diastolically-phased pulsed (DPP) infusions of methotrexate (MTX). Also, pre- and post-disruption permeabilities were assessed in normal brain tissue and in tumor by measuring uptake of Rubidium (Rb) using PET. Results indicate a transient increase in tumor permeability of approximately two fold with a half life of 7 minutes, and a four to five fold increase in permeability in surrounding normal brain tissue of comparable duration.
