Abstract 18537: Erythrocyte Rich Thrombi Reduce Everolimus Diffusion in Thrombus and Arterial Wall ex vivo
Introduction: Drug eluting stents (DES) used to treat acute myocardial infarction, are often placed on thrombus. Mathematical modelling indicates that thrombus acts as a barrier for local drug delivery. However, its composition and age have not been taken into account. We therefore studied diffusion of Everolimus in fresh (FT) and aged thrombus (AT) of different composition, and measured its effect on arterial drug delivery by ex-vivo stenting of porcine coronary arteries.
Methods: Porcine arterial thrombi were formed in vitro from full blood under continuous flow using CaCl2, creating FT (1 day, n=16) and AT (5 days, n=16). Thrombi were incubated in 100μg/ml Everolimus for 15 - 120 minutes to determine drug diffusion using imaging mass spectrometry. Sections were stained by HE to determine porosity, defined as % tissue free space. Ex-vivo stenting with Everolimus DES on mural thrombus was performed in a perfusion chamber using porcine coronary arteries, blood and a heart-lung machine (n=6).
Results: Fibrin rich areas were more porous than erythrocyte rich areas in FT (80.9±8.3% vs. 22.5±13.1%) and AT (73.5±9,2% vs. 3.7±7.6%), all p< 0.001. Faster diffusion (Fig. 1) was observed in fibrin than in erythrocyte rich areas (3.24·109 m2/s vs. 2.13·109 m2/s in FT and 7.35·109 m2/s vs. 0.65·109 m2/s in AT). Fibrin rich areas in AT had the greatest capacity to absorb drugs, despite lower porosity than FT suggesting that diffusion is not merely dependent on porosity. RBC rich had less capacity to absorb Everolimus in both FT and AT (p<0.001). Perfusion experiments showed that abluminal erythrocyte rich thrombus indeed resulted in reduced Everolimus concentrations in the arterial wall (1.7±1.5μg/ml vs. 5.8±4.1μg/ml, p< 0.001) at 5 hours post stenting.
Conclusions: Fibrin rich areas absorb and retain drug well while erythrocyte rich areas show significantly lower absorbing capacity in both fresh and aged thrombi, resulting in decreased arterial drug delivery.
Author Disclosures: A.S. Autar: None. E. Peschier: None. Y. den Hartog: None. V. Van Steijn: None. D.J. Duncker: None. H.M. Van Beusekom: None.
- © 2016 by American Heart Association, Inc.