Abstract 10643: Important Role of Adventitial Vasa Vasorum in the Pathogensis of Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs in Vivo
Background: We tested our hypothesis that the adventitial vasa vasorum (VV) is substantially involved in coronary vasomotor dysfunction induced by drug-eluting stents (DES) in pigs in vivo.
Methods and Results: Sirolimus-eluting stents (SES, 1st generation DES) and biolimus A9-eluting stents (BES, new generation DES) were randomly implanted into the left anterior descending and circumflex coronary arteries in the same pig (n=9). After 1 month, coronary responses were examined by intracoronary serotonin (5-HT, 10 and 100 μg/kg) before and after hydroxyfasudil (HF, a selective Rho-kinase inhibitor, 30 and 100 μg/kg/min), bradykinin (0.1 μg/kg) before and after NG-monomethyl-L-arginine (1 mg/kg), and nitroglycerin (10 μg/kg). After euthanasia, stented vessels were isolated for micro-computed tomography (micro-CT) and immunostainings for Rho-kinase activation, VV and inflammation of the stent edges (vasomotor dysfunction sites). Coronary vasoconstricting responses to 5-HT (100 μg/kg) were significantly reduced at the BES edges as compared with the SES edges (SES; 52±7% vs. BES; 22±3%, P<0.01), and were abolished by HF, whereas coronary vasodilating responses were all comparable. Micro-CT imaging showed that VV was dramatically augmented at the SES site, extending to the proximal and distal portions, which was less evident at the BES site (Figure ). Rho-kinase activity (semi-quantitatively evaluated as in Grade 0-3), VV density and macrophage number in the adventitia were all significantly less at the BES site as compared with the SES site (SES, 2.3±0.2 vs. BES, 1.7±0.1, P<0.01; SES, 79±8 vs. BES, 33±14 P<0.01; SES, 48±9 vs. BES, 23±7, P<0.05, respectively). There was a significant positive correlation between vasoconstriction to 5-HT and VV density (R=0.59, P<0.01).
Conclusions: These results indicate that VV is substantially involved in the DES-induced coronary vasomotor dysfunction through Rho-kinase activation in pigs in vivo.
- © 2013 by American Heart Association, Inc.