Abstract 12800: Beneficial Effects of Polymer-Free Biolimus-Eluting Stents on Coronary Vasomotion in Pigs in Vivo -Possible Involvement of Rho-kinase Inhibition-
Background: The late adverse effects of the 1st generation drug-eluting stents (DES), such as sirolimus-eluting stents (SES), include late stent thrombosis and coronary hyperconstricting responses. We have recently demonstrated that Rho-kinase activation is substantially involved in the latter responses, for which the polymer coating may play a causative role. In this study, we thus examined whether the new generation biolimus-eluting stent with biodegradable polymer coating (BES) has improved property on coronary vasomotion as compared with SES in pigs in vivo, and if so, whether Rho-kinase pathway is involved.
Methods: BES and SES were randomly implanted into the left anterior descending and circumflex coronary arteries in the same male Göttingen miniature pig (n=14). At 1 and 3 months, we examined coronary responses to intracoronary serotonin (10 and 100 μ g/kg) before and after hydroxyfasudil (a specific Rho-kinase inhibitor, 30 and 100 μ g/kg/min dic), bradykinin (BK, 0.1μ g/kg ic), BK after NG-monomethyl-L-arginine (1 mg/kg ic), and nitroglycerin (NTG, 10μ g/kg ic). Changes in coronary diameter from baseline were calculated by quantitative coronary angiography. Histological analyses were performed for the extent of inflammatory responses and microthrombus formation around stent struts (grade from 0 to 3).
Results: At 1 month, coronary vasoconstricting responses to serotonin (100 μ g/kg ic) were significantly reduced at the BES site as compared with the SES site (BES 22±10 vs. SES 54±24%, P<0.01, n=8 each), which was abolished by pre-treatment with hydroxyfasudil. Importantly, the same findings were also observed at 3 months (BES 18±12 vs. SES 36±16%, P<0.05, n=8 each). In contrast, coronary vasodilating responses to BK and NTG were comparable between the 2 groups. The extent of inflammatory responses and microthrombus formation were significantly attenuated at the BES site compared with the SES site (BES 1.08±0.33 vs. SES 1.90±0.62, P<0.01 and BES 0.44±0.52 vs. SES 1.63±0.79, P<0.01, respectively, n=6 each).
Conclusions: These results indicate for the first time that BES inhibits coronary hyperconstricting responses for a long period as compared with SES in pigs in vivo, for which inhibition of the Rho-kinase pathway may be involved.
- © 2012 by American Heart Association, Inc.