title: An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall.
abstract: A venous blood sample taken at autopsy cannot be considered to represent the antemortem blood concentration of a particular substance. Autolytic 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 experimental design represents an in vitro postmortem simulation of a drug substance crossing a venous wall. The postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sampling was restricted to selected autopsy cases. Parameters for the analysis of diffusion across the vascular tissue were dependence on time, temperature, and initial substance concentrations. The penetration behavior simulating venous efflux and influx of the substances was studied by different orientation of the venous wall in the experiments. Rhodamine B was used as a model substance to visualize the binding to the tissue and the passage across the venous wall. The permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wall and on the postmortem time period as well as on concentration gradients. From the data of this preliminary in vitro study, it can be concluded that a lag time for transvascular diffusion exists postmortem. However, it could be demonstrated, that adsorption to and penetration into the vascular tissue may alter intraluminal blood concentrations even at an early stage of the postmortem time period.
authors.affiliation: Institute of Forensic Medicine, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Skopp
authors.forename: R
authors.initials: R
authors.lastname: Lutz
authors.forename: L
authors.initials: L
authors.lastname: Pötsch
authors.forename: B
authors.initials: B
authors.lastname: Ganssmann
authors.forename: K
authors.initials: K
authors.lastname: Klinder
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: R
authors.initials: R
authors.lastname: Aderjan
authors.forename: R
authors.initials: R
authors.lastname: Mattern
mesh_terms: D001692:Biological Transport; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D009020:Morphine / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000493:pharmacokinetics*; D011180:Postmortem Changes; D012235:Rhodamines; D014682:Vena Cava, Inferior / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D009022:Morphine Derivatives; D012235:Rhodamines; C035349:morphine-6-glucuronide; D009020:Morphine; C029773:rhodamine B; C018108:morphine-3-glucuronide