Physical models of vascular systems are being used to study: (1) hemodynamic flow in coronary arteries; and (2) intracarotid infusions of methotrexate following bloodbrain barrier disruption with hypertonic mannitol. (1) The onset of turbulence during oscillating flow has been studied in a series of straight, rigid tubes. An empircal 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, and turbulence correlations were also derived for this situation. (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 postdisruption permeability was assessed in normal brain tissue and in tumor by measuring uptake of Rubidium (Rb) using PET. Preliminary analysis of the results to date indicate a transient increase in tumor permeability of approximately 50% that lasts for 15 minutes, and a three fold increase in permeability in surrounding Normal brain tissue of comparable duration.
