AN IN-VITRO EXPERIMENT FOR POSTMORTEM VASCULAR PERMEATION - THE PASSAGE OF MORPHINE AND MORPHINE GLUCURONIDES ACROSS A VASCULAR WALL

A venous blood sample taken at autopsy cannot be considered to represe nt the antemortem blood concentration of a particular substance. Autol ytic processes cause disintegration and increasing permeability of the physiological and anatomical barriers such as vascular walls and lead to changes in substance concentrations. In the present study, the exp erimental design represents an in vitro postmortem simulation of a dru g substance crossing a venous wall. The postmortem behavior of morphin e, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Va lia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sa mpling was restricted to selected autopsy cases. Parameters for the an alysis of diffusion across the vascular tissue were dependence on time , temperature, and initial substance concentrations. The penetration b ehavior simulating venous efflux and influx of the substances was stud ied by different orientation of the venous wall in the experiments. Rh odamine B was used as a model substance to visualize the binding to th e tissue and the passage across the venous wall. The permeation of mor phine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wa ll and on the postmortem time period as well as on concentration gradi ents. From the data of this preliminary in vitro study, it can be conc luded that a lag time for transvascular diffusion exists postmortem. H owever, it could be demonstrated, that adsorption to and penetration i nto the vascular tissue may alter intraluminal blood concentrations ev en at an early stage of the postmortem time period.