Nitinol stents are widely used for the treatment of peripheral arterial diseases in lower extremity arteries and have shown different clinical outcomes depending on implanted arterial segments. We aimed to compare histopathological responses to nitinol stents in femoral artery (FA) with those in femoropopliteal artery (FPA), which is markedly bended during knee flexion. A single nitinol stent was implanted in FA and FPA of 21 domestic swine. The stented vessels were angiographically assessed and then harvested for histopathology at 1 and 3 months after implantation. Angiographic late lumen loss was significantly greater in FPA than in FA at 3 months. Neointimal area decreased in FA and increased in FPA from 1 to 3 months. Compared with FA, peri-strut area of FPA showed more pronounced hemorrhage and fibrin deposition at 1 month and angiogenesis and inflammation at 1 and 3 months. Injury to internal elastic lamina or media was minimal in both FA and FPA at both time points. In conclusion, vascular responses to nitinol stents were different between FA and FPA with respect to time course of neointimal formation and progress of healing, suggesting that repetitive interaction between stent and vessel wall during dynamic vessel motion affected vascular responses.

Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.

We have developed a new method for obtaining information on whole tissues by light microscopy (LM) and ultrastructural features by transmission electron microscopy (TEM). This method uses serial sections of a stented artery embedded in resin. Stents were implanted in porcine coronary arteries in this study. The heart was perfusion fixed in a 2% paraformaldehyde and 1.25% glutaraldehyde mixed solution. The stented artery was then removed, fixed in 1% osmium, embedded in Quetol 651 resin, and sectioned serially. For LM, the black color of osmium was removed from the section by immersion in periodic acid and hydrogen peroxide after deplasticization. These sections were stained with hematoxylin and eosin and Elastica–Masson trichrome stain. For TEM, thin sections were re-embedded in Quetol 812 resin by the resupinate method and cut into ultrathin sections. A clear, fine structure was obtained, and organelles, microvilli, and cell junctions in the endothelium were easily observed. The combined observation of adjacent specimens by LM and TEM enabled us to relate histopathological changes in the millimeter scale to those in the nanometer scale.

Background The BP-SES has an abluminally applied biodegradable polymer that is fully resorbed after 3–4 months but may have longer-lasting effects. The aim of this study was to determine the long-term vascular response to the novel Ultimaster™ sirolimus-eluting stent (BP-SES). Methods BP-SESs, everolimus-eluting stents (DP-EESs), and bare metal stents were implanted in 22 coronary arteries of 15 mini-swine. All animals underwent optical frequent domain imaging (OFDI) to assess neointimal volume and quality at either 1 (n = 7) or 3 (n = 8) months and at 9 (n = 15) months and were euthanized at 9 months. Stents were subsequently histologically investigated to analyze the vascular response and maturity of neointimal tissue according to cell density. Results OFDI revealed greater regression in neointimal volume from 3 to 9 months with BP-SESs than with DP-EESs (−0.6 ± 0.5 mm 2 vs. 0.00 ± 0.4 mm 2 , p = 0.07). Although there was no significant difference between BP-SESs and DP-EESs in the inflammation score (BMS, BP-SES, and DP-EES: 0.1 ± 0.1, 0.3 ± 0.4, and 0.4 ± 0.4, respectively; p < 0.0001) in histological analysis, BP-SESs showed slightly greater maturity than DP-EESs (1.8 ± 0.3, 1.7 ± 0.3, and 1.6 ± 0.3, p = 0.09). Conclusions While both BP-SESs and DP-EESs showed minimal inflammatory responses at 9 months, BP-SESs showed a trend for greater neointimal maturity and regression, which may be related to earlier completion of the vascular response.

The aim of this study was to identify potential changes that could occur during histological evaluations of CLAWN miniature swine, with potential consequences for subsequent experiments. The systemic organs from male and female CLAWN miniature swine (16.3–42.3 months old) that had been used in long-term studies of coronary stent implantation were examined histologically. Commonly observed histopathological findings were testicular/epididymal atrophy, cyst-like follicles in the ovaries, hemosiderin deposition in the spleen, lipofuscin deposition in the proximal tubular epithelia and presence of eosinophilic globules in the Bowman’s space and the lumen of the proximal tubules in the kidneys, and cellular infiltration in several organs, including the eyelids, respiratory organs, and digestive tract. However, none of these changes were serious enough to indicate a significant impact on research. In conclusion, this study identified CLAWN miniature swine as a suitable animal model for various experiments.