MIT scientists including Elazer R. Edelman, the Thomas D. and Virginia W. Cabot Professor of Health Science and Technology (HST), and HST postdoctoral associate Vijaya B. Kolachalama, developed computer models to predict physiologically realistic drug delivery patterns from stents in branched arterial vessels. They simulated several arterial settings to show that drug distribution in these situations is determined by a complex calculation of the stent's position relative to arterial branches and constant blood flow changes caused by the branching.
"We now demonstrate for the first time that spatial variation in drug distribution can be significant when appreciated from a three-dimensional perspective and this viewpoint can only be gained with the use of these model systems," said Edelman.
Drug-eluting stents are now widely used all over the world to treat obstructive arterial disease, yet some patients with the stents have suffered life-threatening side effects: an increase risk of blood clotting and heart attacks. Several important questions remain unanswered - in particular, the mechanisms that govern drug delivery to specific lesion sites are poorly defined and pose challenges for stent designers, physicians, and regulatory agencies that must evaluate stents' safety and efficacy.
Predicting drug distribution is complicated by the branching of arteries into two or more vessels, which establishes alterations in flow, wall shear stress and geometries. All of those can be modeled and defined mathematically, however, the variations cannot be captured across the full spectrum of perturbations and combinations in animal systems or in the lab, let alone the human. Computational models are therefore required.
"By observing the arterial drug distribution patterns for various settings, we understood that drug released from the stent does not reach uniformly to all regions of the vessel and this non-uniformity depends on where the stent is placed in the artery as well as the blood flow that is entering the vessel," says Edelman. "Appreciating this phenomenon for more complex cases like branched vessels is non-intuitive, but now we have a computer model that gave us the much needed insight."