Pathological findings after third- and second-generation everolimus-eluting stent implantations in coronary arteries from autopsy cases and an atherosclerotic porcine model

Figures

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  Figure 1. Pathology of human autopsy cases. (A–N) Representative images of human coronary arteries with implanted third-generation abluminal biodegradable-polymer everolimus-eluting stents (3rd EES, A–G) and second-generation durable-polymer everolimus-eluting stents (2nd EES, H–N). (A) Most struts of the 3rd EES are covered with neointima. (B–D) The neointima after 3rd EES implantation shows a well-developed matrix with tightly arranged smooth muscle cells. There is no infiltration of inflammatory cells. (E) The luminal surface is well-covered by endothelial cells (arrows). (F, G) Few fibrin deposits are observed around the 3rd EES struts. (H, J) Some struts of the 2nd EES are not covered. (I) Neointima after 2nd EES implantation consists of loose connective tissue. (K) Advanced inflammatory cell infiltration and fibrin deposits (arrows) are seen around the struts of the 2nd EESs. (L) Advanced inflammatory cell infiltration and neointima partially lacking endothelial cells (arrows) are shown. (M, N) Fibrin deposition is prominent around the 2nd EES struts. (O) Morphometrical analysis of the 3rd and the 2nd EES tissues. Although both 3rd and 2nd EESs show a high degree of coverage, the 3rd…

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  Figure 2. Optical coherence tomography images and pathology of the 4-week stent lipoprotein receptor knockout minipigs. Representative images from the 4-week group of coronary arteries of lipoprotein receptor knockout minipigs implanted with third-generation abluminal biodegradable-polymer everolimus-eluting stents (3rd EES, A–C) and second-generation durable-polymer everolimus-eluting stents (2nd EES, D–F). (A, D) On optical coherence tomography, all struts of both 3rd and 2nd EESs were shown to acquire adequate neointimal coverage. Histological sections of coronary arteries implanted with 3rd (B, C) and 2nd (E, F) EESs. Underlying atherosclerotic change with extracellular lipid accumulation (C), foam cell infiltration (arrowheads in F) and calcification (arrows in F) are apparent. The neointima of the 3rd EES showed tightly arranged smooth muscle cells close to the luminal surface (B) while the neointima over 2nd EESs consisted of poorly structured connective tissue (E). (G) There is significantly less neointimal thickening and fewer fibrin depositions with the 3rd EES than with the 2nd EES. †p < 0.05 (B *; stent strut. B, C, E, F; hematoxylin–eosin).

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  Figure 3. Neointimal tissue characteristics of the 4-week stent implantation group of low-density lipoprotein receptor knockout minipigs. (A–D) High-power magnification images of the neointima from the 4-week group of coronary arteries of low-density lipoprotein receptor knockout (LDLR −/−) minipigs implanted with the third-generation abluminal biodegradable-polymer everolimus-eluting stents (3rd EES, A, C) and second-generation durable-polymer everolimus-eluting stents (2nd EES, B, D) (upper panel: Hematoxylin–eosin, middle panel: alpha-Smooth muscle actin, lower panel; acian-blue). (A, B) Show the neointima above stent struts and (C, D) show the neointima distant from the stent struts. The part above the dotted line corresponds to the neointima and the part below to the intima and media. (A, C) Neointima after the 3rd EES shows several compact layers of tightly arranged smooth muscle cells (SMCs), close to the luminal surface. (B, D) Neointima after the 2nd EES. Although thicker than that seen after the 3rd EES implantation, the neointima consists of proteoglycan-rich tissue and its density of SMCs is relatively low. (E) Neointima above the stent struts of the 3rd EES demonstrated…

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  Figure 4. Protocols for animal experimentation and morphometrical analysis. (A) Outline of low-density lipoprotein receptor knockout (LDLR −/−) minipigs experiment. (B–E) Images of coronary arteries from LDLR −/− minipigs before stent implantation. (B) Angiographically, mild stenosis due to arteriosclerosis is visible. (C–E) Eccentric fibro-fatty plaques (arrows) are observed on intravascular ultrasound. (F–I) Grading of peri-strut inflammation for semi-quantitative analysis. (F) Grade 0, absent, few inflammatory cells. (G) Grade 1, mild, fewer than 20 inflammatory cells per high power field (HPF). (H) Grade 2, moderate, fewer than 50 inflammatory cells per HPF. (I) Grade 3, severe, more than 50 inflammatory cells per HPF. (J) Tissue characteristics are evaluated for the neointima above the stent strut and the neointima distant from the stent struts. (K, L) All sections of stented regions harvested from porcine coronary arteries are immunostained for anti-CD31 antibody. The total luminal circumference (K) was measured and the lengths of re-endothelialized regions (arrows in L) were added up. The ratio of the re-endothelialized region was calculated (F–J; hematoxylin–eosin, K, L;…