Vascular Responses to Drug-Eluting and Bare Metal Stents in Diabetic/Hypercholesterolemic and Nonatherosclerotic Porcine Coronary Arteries

Abstract

Background-Animal models used to gain insight into the vascular response to drug-eluting stents are generally juvenile and nonatherosclerotic, whereas stents are placed in patients with complex atherosclerosis and comorbidities. Hence, models reflecting these complexities are needed to help elucidate the vascular effects of drug-eluting stents. We compared the vascular responses with bare metal stent (BMS) and paclitaxel-eluting stent (PES) implantation in a diabetic/hypercholesterolemic (DM/HC) porcine model of advanced coronary atherosclerosis with the standard juvenile porcine model. Methods and Results-Two studies using similar stent procedural protocols were performed in either DM/HC (nϭ20) or domestic swine (non-DM/HC, nϭ20). Animals pretreated with dual-antiplatelet therapy, underwent BMS or PES implantation (1/artery, 2 stents per animal) and were euthanized 30 or 90 days later. DM/HC resulted in a 24% increase in platelet aggregation (Pϭ0.05 versus baseline), whereas dual-antiplatelet therapy reduced platelet aggregation in both groups (PϽ0.0001). DM/HC pigs developed substantially greater neointimal area versus non-DM/HC pigs, regardless of stent type, (Pϭ0.004 for BMS at 30 days and Pϭ0.002 at 90 days, Pϭ0.005 for PES at 30 days, Pϭ0.002 at 90 days). Compared with non-DM/HC pigs, reendothelialization was delayed in DM/HC pigs, more so after PES implantation. Increased para-strut leukocytes were observed for PES compared with BMS in the DM/HC pigs at both 30 days (Pϭ0.023) and 90 days (Pϭ0.04). As well, increased T-lymphocyte infiltration was seen in the DM/HC pigs. Conclusions-Stent implantation in a DM/HC swine model provides a metabolic environment closer to human disease, including hyperglycemia, hypercholesterolemia, and increased platelet aggregation. This model augmented differences in the vascular response between PES and BMS that are not as clearly evident in the non-DM/HC swine, including increased neointimal area, delayed reendothelialization, and greater, persistent vascular inflammation. (Circ Cardiovasc Interv. 2011;4:438-446.)

Impact of prior intracoronary stenting on late outcomes of coronary artery bypass surgery in diabetics with triple-vessel disease

“…In diabetics with an inherently compromised endothelial function 19 and an increased propensity for inflammation, 20 the above processes may be magnified. 29 Together, increased inflammation and endothelial dysfunction can jeopardize graft patency and negatively affect CABG outcomes, as reported in a recent small study showing a trend toward reduced patency of grafts from the internal thoracic artery to the left anterior descending artery in patients with left anterior descending artery stents. 18 …”

Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

“…The vascular effects of both drug-eluting and bare-metal stenting in DM/HC porcine coronary arteries were examined and compared to implantation in nonatherosclerotic porcine arteries [18]. Increased neointimal accumulation and vascular inflammation following both bare metal and paclitaxel eluting stent implantation were observed in DM/HC swine, and use of the DM/HC model allowed for greater discrimination of the vascular effects of bare metal and drug eluting stents compared to nonatherosclerotic porcine model.…”

Comparison of dedicated BIOSS bifurcation stents with regular drug-eluting stents for coronary artery bifurcated lesions: Pooled analysis from two randomized studies

“…Interestingly, this study obtained numerically better results for BiOSS than in rDES subgroups in cases of patients with DM. Vascular response in patients with DM and dyslipidemia differ significantly when compared with healthy controls in terms of increased neointimal area, delayed reendothelialization, and greater, persistent vascular inflammation [18]. Nevertheless, data suggest that DM and non-DM lesions showed similar vessel response in both in-stent and reference segments, regardless of the DES type [19].…”