In vitro evaluation of vascular permeability to contrast media using cultured endothelial cell monolayers.
OBJECTIVE
The efficiency of contrast agents in medical imaging depends on their distribution into vascular and interstitial compartments. The aim of this study was to compare in vitro endothelial permeability to different classes of contrast agents with various vascular persistence properties: a triiodinated nonionic monomer (ioversol), an iodinated dextran polymer (P604), and an iron oxide nanoparticle (sinerem).


METHODS
Permeability studies, through collagen-coated filters with or without porcine aortic endothelial cell monolayer, were carried out by placing each filter-ring (luminal chamber) into a beaker containing a culture medium (abluminal chamber). Contrast media, diluted in the culture medium, were added to the luminal chamber. Aliquots were sampled from the abluminal chamber for contrast agent determinations. The volume cleared of the compound was calculated from the luminal side to the abluminal side. Parallel permeability tests to [3H]-H2O and Evans blue albumin were performed as references. Finally, the modulatory effect of bradykinin on endothelial permeability to albumin or to contrast agents was studied.


RESULTS
The volume cleared of ioversol, P604, and sinerem through membrane filters was decreased by 19.6%, 32.1%, and 52.0%, respectively, in the presence of a cell monolayer. Bradykinin (10(-6) M) significantly increased permeability to albumin, ioversol, and sinerem. Ioversol and sinerem induced a significant decrease in permeability to albumin.


CONCLUSIONS
A relation between the molecular size of the contrast agents tested and their endothelial permeability can be established with this in vitro model.
Martin-Chouly
C A
CA
Laboratoire de Pharmacologie moléculaire, Université de Rennes I, France.
Youmine
H
H
Saiag
B
B
Hentsch
A M
AM
Corot
C
C
Legrand
A
A
D000704:Analysis of Variance; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D052203:Ferrosoferric Oxide; D007501:Iron / Q000494:pharmacology*; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000494:pharmacology*; D013552:Swine; D014283:Triiodobenzoic Acids / Q000494:pharmacology*
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C401208:P604 polymer; D014283:Triiodobenzoic Acids; C097921:ferumoxtran-10; D007501:Iron; C054871:ioversol; D001920:Bradykinin; D052203:Ferrosoferric Oxide