Thrombus causes fluctuations in arterial drug delivery from intravascular stents.
Arterial drug concentrations determine local toxicity. As such the emergent safety concerns surrounding drug-eluting stents mandate an investigation of the factors contributing to fluctuations in arterial drug uptake. Drug-eluting stents were implanted into porcine coronary arteries, arterial drug uptake was followed and modeled using 2-dimensional computational drug transport. Arterial drug uptake in vivo occurred faster than predicted by free drug diffusion, thus an alternate, mechanism for rapid transport has been proposed involving carrier-mediated transport. Though there was minimal variation in vivo in release kinetics from stent to stent, arterial drug deposition varied by up to 114% two weeks after stent implantation. The extent of adherent mural thrombus also fluctuated by 113% within 3 days after implantation. The computational drug transport model predicted that focal and diffuse thrombi elevate arterial drug deposition in proportion to the thrombus size by reducing drug washout subsequently increasing local drug availability. Fluctuations in arterial drug uptake are commonly reported. We now explain that variable peristrut thrombus can explain such observations even in the face of a narrow range of drug release from the stent. The mural thrombus effects on arterial drug deposition may be circumvented by forcing slow, rate limiting arterial transport that cannot be further hindered by mural thrombus.
Balakrishnan
Brinda
B
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. innga@mit.edu
Dooley
John
J
Kopia
Gregory
G
Edelman
Elazer R
ER
D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D002317:Cardiovascular Agents / Q000008:administration & dosage; D023903:Coronary Restenosis / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D016503:Drug Delivery Systems; D054855:Drug-Eluting Stents; D020123:Sirolimus / Q000008:administration & dosage; D013552:Swine; D013556:Swine, Miniature; D013927:Thrombosis / Q000473:pathology*; D013997:Time Factors
D002317:Cardiovascular Agents; D020123:Sirolimus