O implante de stents em região vascular periférica tem sido apontado como uma solução para o tratamento endovascular, e tem sido largamente utilizado. No entanto, há estudos que apontam com certa frequência a ocorrência de problemas ligados a fraturas de stents, as quais devem ser diagnosticadas e convenientemente tratadas. Na região femoropoplítea, por exemplo, foi detectada a ocorrência de 32% de fraturas em um conjunto de 121 tratamentos, conforme aponta pesquisa realizada. O diagnóstico de tais fraturas é normalmente feito a partir de análise visual de imagens, as quais muitas vezes apresentam ruídos e deformidades decorrentes do método empregado para a sua captura, dificultando a correta visualização de sua estrutura e deformidades. A escassez de recursos e estudos que permitam a automatização deste processo motivaram a realização deste trabalho, em que são desenvolvidas técnicas que melhoram a visualização dos elementos de imagem de forma a facilitar o diagnóstico de observação e, quando possível, apontar regiões de possíveis fraturas. Para isto, a utilização de elementos computacionais clássicos e o desenvolvimento de técnicas adicionais inéditas contribuem para a análise de imagens, fornecendo um possível direcionamento como forma de auxílio ao diagnóstico médico. Os métodos desenvolvidos são aplicados a amostras de imagens, e os resultados obtidos são comparados àqueles do diagnóstico médico. Como resultado obteve-se, além da melhoria de visualização das imagens, um índice de concordância Kappa de 0,878 para a detecção de fraturas, o que confirma o método como satisfatório e de concordância bastante relevante. / The insert of stents in peripheral vascular region has been considered as a solution for endovascular treatment, and has been widely used. However, there are studies that show, with a certain frequency, the occurrence of problems related to stent fractures, which should be diagnosed and properly treated. In the femoropopliteal region, for example, it was detected 32% of fractures in a set of 121 treatments, as shown by survey. The diagnosis of such fractures is usually made from visual analysis of images, which often shows noise and deformation resulting from the method employed for capture, making difficulty to the correct visualization of its structure and deformities. The lack of resources and studies that allows to automate this process, motivated this work, in which techniques are developed that improve the display of the image elements in order to facilitate the diagnosis by observation and, when possible, pointing out areas of possible fractures. For this, the use of classical elements and the development of additional computational techniques contribute to innovate image analysis, providing a possible direction as a way to aid medical diagnosis. The developed methods are applied to images samples and the results are compared to those of medical diagnosis. As a result obtained, as well as the improved display of images, a Kappa concordance index of 0.878 for the detection of fractures confirms the method as satisfactory and a quite relevant agreement.

La perturbation des écoulements au voisinage de la paroi artérielle équipée d'un stent joue un rôle prépondérant dans l'apparition et le développement des complications liées aux maladies cardiovasculaires (sténose, resténose, thrombose...). La topologie de l'écoulement dans ces régions est très complexe. En effet, au voisinage du stent, des zones de recirculation se forment en amont et aval de chaque branche et les contraintes pariétales y sont très faibles. Des études in vivo et in vitro ont mis en évidence le rôle de ces caractéristiques de l'écoulement intra-stent sur les maladies cardiovasculaires. Pour cela, la bonne estimation des contraintes pariétales et la compréhension du comportement de l'écoulement intra-stent et son rôle dans le transfert du principe actif devraient permettre d'optimiser les traitements (design de la prothèse, principe actif...). L'approche numérique est une voie très utile pour étudier ces phénomènes. Cependant, la bonne précision du calcul dépend du choix du modèle d'écoulement, des conditions aux limites, de la géométrie du stent et de l'artère pour réaliser une simulation pertinente.Nous étudions ici dans un premier temps l'effet du choix du modèle hémodynamique sur les caractéristiques de l'écoulement intra-stent. Trois modèles numériques décrivant l'écoulement coronaire ont été utilisés. Ces modèles sont : un modèle stationnaire "MP", le modèle pulsé simplifié "MPS" et le modèle pulsé complet "MPC" basé sur l'analyse de Womersley. Nous avons ainsi montré l'importance de la prise en compte de l'instationnarité de l'écoulement mais au dépens d'un temps de calcul très accru. Dans un second temps, nous étudions expérimentalement l'écoulement intra-stent en utilisant la technique de mesure "PIV". Cette étude expérimentale a permis de confirmer les résultats numériques précédents. Au final, nous examinons numériquement l'effet de la pulsatilitié de l'écoulement sur les flux massiques libérés par les faces d'une branche de stent actif. Cette étude numérique a mis en exergue l'importance du couplage entre les recirculations et le transfert de masse vers la paroi artérielle. / The disturbance of the flow in the vicinity of the arterial wall equipped with a stent plays a key role in the onset and development of complications related to cardiovascular diseases (stenosis, restenosis, thrombosis...). The topology of the flow field in the intra-stent zone is very complex. Indeed, in the vicinity of the stent, recirculation zones form upstream and downstream of the stent strut where wall shear stress is very low. In vivo and in vitro studies have demonstrated the role of the in-stent flow features on cardiovascular diseases.The correct estimation of the wall shear stress, the understanding of the behavior of the in-stent flow and its role in the transfer of the drug are expected to help optimize treatments (stent geometry, drug composition...). The numerical approach (CFD) is a useful and versatile way to study these phenomena. However, the accuracy and the relevance of the results depend on the choice of the flow model, the boundary conditions and the stent and artery geometry.Firstly we study in this work the impact of the hemodynamic model on the in-stent flow characteristics. Three numerical models describing the coronary flow are used. These models are: the steady model "MP", the simplified pulsatile model "MPS" and the complete pulsatile model "MPC" based on Womersley's analysis. We show the importance of the pulsatility of the flow but at the expense of a high increase in the computing time. Secondly we study experimentally the in-stent flow using measurement technique "PIV". This experimental study confirms the previous numerical results. Finally we examine numerically the effects of the flow pulsatility on the mass fluxes released by the faces of a drug eluting stent. This numerical study highlights the importance of the coupling between the recirculation zones and the mass transfer into the arterial wall.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12999号 / 論医博第2107号 / 新制||医||1016(附属図書館) / 32927 / (主査)教授 川上 浩司, 教授 古川 壽亮, 教授 小池 薫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No / To assess the technical success rate, and evaluate the clinical outcome, length of hospital stay, and cost of palliative gastro-duodenal stenting in a single-centre. Materials and methods Eight-seven patients referred for insertion of a gastroduodenal stent between April 1999 and April 2004 were recruited to a non-randomized, before and after intervention study performed in a single centre. Demographic data, diagnosis and symptoms along with clinical and technical outcomes were recorded. Results The technical success rate was 84/87 (96.6%), with inability to traverse the stricture in three patients. No immediate complications were demonstrated. There was marked improvement after stent placement with resolution of symptoms and commencement of dietary intake in 76 patients (87%). Stenting resulted in improved quality of life as reflected by an increase in Karnofsky score from 44/100, to 63/100 post-procedure. Late complications included perforation (n=1), migration (n=1) and stent occlusions due to tumour ingrowth/overgrowth (n=7; mean 165 days). Mean survival was 107 days (range 0¿411 days). Median hospital stay post-stent placement was 5.5 days, (range 1¿55 days) with a majority of patients (75%) discharged home. The mean cost of each treatment episode was £4146 ($7132 $US, ¿6,028 EUROS). Conclusion The present series confirms that combined endoscopic and radiological gastroduodenal stenting is a highly favourable treatment for patients with inoperable malignant gastric outlet obstruction. The results suggest that this minimally invasive procedure has a very high technical success rate, whilst at the same time providing excellent palliation of symptoms with improved quality of life in the majority of patients.

<p>ZIEL:<br>Untersuchung des Auftretens von In-Stent-Restenosen (ISR) nach stentgeschützter perkutaner transluminaler Angioplastie intrakranieller Stenosen.</p><p> METHODEN:<br> In diese retrospektive Langzeit-Follow-up-Studie wurden konsekutiv 46 Patienten mit insgesamt 49 intrakraniellen Stenosen eingeschlossen, die im Zeitraum von August 2003 bis Juli 2010 mittels Stentangioplastie behandelt wurden. Der Nachbeobachtungszeitraum erstreckte sich bis Februar 2011. Die Quantifizierung der Stenosen erfolgte an angiografischen Bildern. Als ISR wurde eine erneute Stenose >50% innerhalb des Stents oder unmittelbar (d.h. innerhalb von 5mm) neben dem Stent und einem absoluten Lumenverlust von >20% definiert. Die Mittelwerte der Stenosegrade zu unterschiedlichen Zeitpunkten wurden mit dem t-Test für abhängige Stichproben verglichen. Die ISR-freie Überlebenswahrscheinlichkeit wurde mit der Kaplan-Meier-Kurve untersucht und Kurvenvergleiche für Untergruppen erfolgten mit dem Log-Rang-Test.</p><p> ERGEBNISSE:<br> Die mediane Follow-up-Dauer betrug sieben Monate (Spannweite: ein Tag-75 Monate, Interquartilsabstand: 20,25 Monate, Mittelwert: 17,4 Monate). Zwei Patienten verstarben an peri- bzw. post-prozeduralen Komplikationen (eine intrakranielle Blutung aufgrund einer Dissektion mit einem arteriovenösen Shunt und eine Reperfusionsblutung). Sechs Patienten mit sieben behandelten Stenosen verstarben innerhalb des Beobachtungszeitraums ohne bekannte Todesursache. Es gab für 57% der Stenosen mindestens eine Bildgebung im Verlauf. Die 1-Jahres-ISR-freie Überlebenswahrscheinlichkeit für das Gesamtkollektiv lag bei 69%. Insgesamt traten acht ISR auf; sieben davon innerhalb der ersten acht Monate nach Stentplatzierung. Mittels Log-Rang-Test wurde eine signifikant niedrigere 8-Monats-ISR-freie Überlebenswahrscheinlichkeit in der Gruppe der ≤55-jährigen Patienten im Vergleich zu >55-jährigen Patienten (13% versus 79%, p=0,002) ermittelt. Für Patienten ohne eine arterielle Hypertonie resultierte eine signifikant niedrigere 7-Monats-ISR-freie Überlebenswahrscheinlichkeit und eine höhere für Patienten mit einer arteriellen Hypertonie (0% versus 81%, p=0,006). Nur zwei von acht Patienten zeigten zum Zeitpunkt der ISR-Diagnose Symptome. Die Zunahme einer ISR bis zum Gefäßverschluss bei einem Patienten mit einem angiografisch dokumentierten suffizienten Kollateralkreislauf verlief ohne Symptome.</p><p> SCHLUSSFOLGERUNG:<br> Gerade innerhalb der ersten Monate nach stentgeschützter perkutaner transluminaler Angioplastie sind engmaschige Verlaufskontrollen wichtig. Die Festsetzung der Zeitpunkte für Verlaufskontrollen sollte dabei nicht allein auf einer eventuell vorhandenen klinischen Symptomatik basieren. Möglicherweise bilden ≤55-jährige Patienten und Patienten ohne eine arterielle Hypertonie mit höherer Wahrscheinlichkeit eine ISR. ISR können im zeitlichen Verlauf sowohl zu- als auch abnehmen. Der Progress einer ISR bis zum vollständigen Gefäßverschluss kann im Fall einer ausreichenden intrakraniellen Kollateralgefäßversorgung asymptomatisch verlaufen. Somit könnte der zusätzlichen Evaluation des Kollateralstatus in der Verlaufsbeurteilung von ISR ein wichtiger Stellenwert zukommen.</p>

L’angioplastie coronaire est la première forme de revascularisation coronaire. Elle présente cependant 2 limites qui restreignent encore son utilisation : la thrombose et la resténose de stent. La thrombose de stent est un événement précoce associé à une mortalité élevée. Les plaquettes y jouent un rôle déterminant. Le développement de tests fonctionnels plaquettaires permettant d’analyser le niveau de réactivité plaquettaire sous traitement a permis de mettre en évidence les limites de celui-ci sur le plan biologique. Nous avons démontré l’impact clinique de l’utilisation de ces tests dans la prédiction et la réduction du risque de thrombose de stent chez des patients traités par angioplastie coronaire. La resténose est quant à elle une complication tardive de l’angioplastie coronaire avec implantation d’un stent non-actif. Sa physiopathologie repose sur des mécanismes de lésion et de régénération endothéliale. Des marqueurs endothéliaux circulants ont récemment été développés. Nous avons montré qu’ils pouvaient permettre d’évaluer la lésion et la régénération endothéliale induite par une angioplastie coronaire. Les cellules endothéliales circulantes s’élèvent transitoirement après l’angioplastie et ce de façon variable en fonction de la réactivité plaquettaire sous traitement démontrant les interactions étroites entre ces différents acteurs. Dans le même temps, on observe une mobilisation de progéniteurs d’origine médullaire suite à l’angioplastie. Nos travaux suggèrent un rôle clé de la régénération endothéliale dans la cicatrisation vasculaire après angioplastie. En effet, il apparait que la proportion de progéniteurs de profil de différenciation endothélial en réponse à l’angioplastie coronaire détermine la survenue d’une resténose intra-stent. Ces données ouvrent la voie à une meilleure compréhension des mécanismes physiopathologie menant à la resténose mais aussi à des perspectives thérapeutiques intéressantes. / Percutaneous coronary intervention is the most commonly used revascularization technique. However it has 2 main complications limiting its widespread: stent thrombosis and in stent restenosis. Stent thrombosis is an early event associated with a high mortality rate. Platelets are key in its physiopathology. The availability of platelet function tests allowing to determine platelet reactivity levels under therapy showed a variable ant platelet effect following aspirin and clopidogrel intake. We further demonstrated that tailoring anti platelet therapy according to platelet function tests results decrease the rate of stent thrombosis following PCI without increasing bleedings. In stent-restenosis is a late complication of PCI with bare metal stents. The pathophysiology of in-stent restenosis is dependent on the lesion and regeneration of the endothelium. Circulating endothelial biomarkers have recently been developed. We have demonstrated that this marker allow to evaluate the lesion and regeneration of the endothelium following PCI. We evidenced a transient increase in circulating endothelial cells following PCI which is dependent on the level of platelet reactivity inhibition demonstrating the interaction between platelets and the endothelium. At the same time, PCI induces mobilization of progenitor cells which is detectable early after the intervention. Our work suggests that these progenitor cells have a key role in endothelial regeneration after PCI. We evidenced for the first time that the proportion of endothelial progenitor cells among progenitor cells mobilized after PCI determine the occurrence of in stent restenosis. Altogether these data give critical inside into vascular regeneration after PCI in human and on the mechanisms associated with in stent restenosis thus providing new potential therapeutic target.

Introdução: Apesar dos avanços significativos no tratamento endovascular das doenças arteriais coronarianas e periféricas, a reestenose intra-stent continua sendo o principal limitante a médio prazo desses procedimentos. O mecanismo da reestenose intra-stent é principalmente a hiperplasia intimal, já que o stent impede a retração elástica aguda e resiste ao remodelamento geométrico negativo tardio. A hiperplasia intimal ocorre basicamente em resposta à formação de trombo local, à inflamação e às dissecções intimais e mediais secundárias à injúria causada pelo stent, sendo o grau de resposta intimal a base dos efeitos a longo prazo. O uso de stents com hastes menores e revestidos com drogas ou polímeros tem sido considerado uma nova alternativa para a prevenção da reestenose intra-stent. Objetivo: Analisar a resposta arterial ao implante de stent de cromo-cobalto sem e com revestimento de polímero Camouflage® em artérias carótidas de suínos, utilizando os seguintes parâmetros histológicos: grau de endotelização, conteúdo de células musculares lisas, grau de angiogênese, conteúdo de fibrina, grau de inflamação e injúria; além da análise histomorfométrica. Método: Stents balões-expansíveis de cromo-cobalto ( 8 stents CC Flex e 5 stents CC Flex Proactive) de 4 x 16 mm foram implantados em artérias carótidas comuns de oito suínos jovens, sendo um stent liberado em cada artéria. Após 30 dias, as artérias contendo os stents foram removidas, fixadas e coradas pelos métodos de hematoxilina/eosina e Verhoeff/Van Giesson. O segmento arterial contendo o stent foi dividido em 3 blocos distintos: proximal, médio e distal. Os cortes histológicos foram obtidos utilizando-se micrótomo de impacto (Polycut S, Leica, Alemanha) equipado com navalha de tungstênio de 16 cm, tipo D (Leica, Alemanha), com 5 ^m de espessura. A navalha de tungstênio mantém as hastes dos stents intactas nas secções transversas, minimizando os artefatos potenciais causados pela retirada dos stents. A avaliação foi realizada através de critérios histológicos e histomorfométricos. Resultados: Todos os stents foram implantados com sucesso e sem dificuldades técnicas. A análise histológica em 30 dias evidenciou alto grau de endotelização em todos os segmentos avaliados e leve à moderada infiltração de células musculares na íntima. Observou-se baixo grau de angiogênese em cerca de 50% dos segmentos avaliados e ausência completa de deposição de fibrina em pelo menos 80%, com distribuição semelhante entre os grupos. A resposta inflamatória e o grau de injúria causadas pelas hastes dos stents também foram discretas e similares entre os grupos e não houve correlação entre resposta inflamatória e injúria e desses parâmetros com a área de neoíntima. O grau de obstrução neo-intimal identificada neste período foi pequeno (15,1% +/- 8,38 CC Flex x 15,5%+/- 5,39 CC Flex ProActive) e estatisticamente não significativo entre os grupos (p=0,785). Conclusão: Os achados deste estudo experimental sugerem que o uso de stents de cromo-cobalto revestidos com polímero Camouflage® em artérias carótidas de suínos parece estar associado, pelo menos no curto prazo, a uma resposta histológica semelhante àquela encontrada após o implante de stents de cromo-cobalto não revestidos. Neste período não se observou uma menor hiperplasia intimal em virtude do revestimento de polímero. / Introduction: Despite all the advances in the endovascular treatment of coronary and peripheral artery diseases, in-stent restenosis is still the main limiting factor of these procedures in the medium and long-term. The mechanism of in-stent restenosis is mainly the intimal hyperplasia, as the stent prevents acute elastic recoil and later negative geometric arterial remodeling. Intimal hyperplasia occurs basically in response to the formation of local thrombus, inflammation and intimal and medial dissections secondary to the injury caused by the stent, with the degree of intimal response being the cause of long-term effects. Coating drug-eluting stents with polymers and drugs with thinner struts have been considered a new alternative for in-stent restenosis prevention. Objective: Analyse the arterial response to the cobalt-chromium stent implant with and without polymer coating Camouflage® in carotid arteries of pigs, using the following histological parameters: degree of endothelialization, smooth muscle cells (SMC) content, degree of angiogenesis, intimal fibrin content, degree of inflammation and injury; plus histomorphometric analysis. Method: Cobaltchromium balloon-expandable stents (8 CC Flex stents and 5 CC Flex Proactive), 4 x 16 mm, were deployed in common carotid arteries of 8 young pigs, with one stent being deployed in each artery. After 30 days, the arteries containing the stents were removed and underwent fixation and staining using the hematoxilin/eosin and Verhoeff /Van Giesson methods. The arterial segment containing the stent was divided into 3 distinct portions: proximal, middle and distal. The histological sections were obtained using impact microtome (Polycut S, Leica, Germany), equipped with a 16 cm, type D, 5 ^m thick tungsten knife (Leica, Germany). The tungsten knife maintains the stent shaft intact in cross sections, minimizing the potential artifacts caused by stent removal. The evaluation was carried out using histological and histomorfometric criteria. Results: All the stents were deployed with success and with no technical difficulties. The histological analysis performed after 30 days showed a high level of endothelialization in all the evaluated portions and mild to moderate infiltration of the SMC in the intima layer. A low level of angiogenesis of about 50% of the evaluated portions was observed and a complete absence of fibrin deposition in at least 80% of the portions, with similar distribution among the groups. The inflammatory response and the level of injury caused by the struts of the stents were also minimum and this was similar among the groups. There was no correlation between inflammatory response and injury and between the two latter parameters and the neo-intima area. The level of neo-intimal obstruction identified in this period was small (15,1% +/- 8,38 CC Flex x 15,5%+/- 5,39 CC Flex ProActive ) and no statistical significance between the groups (p=0,785). Conclusion: The findings of this experimental study suggest the use of balloonexpandable cobalt-chromium stents coated with polymer Camouflage® in carotid arteries of pigs seems to be associated, at least in the short-term, with a similar histological response to that found in the implantation of non-coated cobalt-chromium stents. In this period, a lower intimal hyperplasia was not observed with polymer coating stents.

Σκοπος της μελέτης είναι να συγκρίνει τις απλές μεταλλικές ενδοπροθέσεις (stents) με τις εσωτερικά και εξωτερικά επικαλυπτόμενες μεταλλικές ενδοπροθέσεις σε πειραματόζωο χοίρο. Τοποθετήθηκαν μεταλλικά stents σε 9 θηλυκούς χοίρους που ζύγιζαν 25-30 κιλά. Τοποθετήθηκαν stent σε 18 ουρητήρες είτε στον δεξιό είτε στον αριστερό ουρητήρα. Σε έξι ουρητήρες τοποθεητήθηκε ενδοπρόθεση Wallstent (Schneider,Zurich,Switzerland)σε έξι τοποθετήθηκε Passager stent (Βoston Scientific, Natick,MA,USA)και σε έξι Corvita endoluminal graft- CEG(Boston Scientific, Natick, MA, USA). Εγινε έλεγχος της βατότητας με νεφροστομογραφία 24ώρες και 21ημέρες μετά την τοποθέτηση. Σε τεσσερεις περιπτώσεις το Passager stent μετανάστευσε στην ουροδόχο κύστη με αποτέλεσμα την ουρητηρική απόφραξη. Σε όλες τις άλλες περιπτώσεις η ροή των ούρων ήταν φυσιολογική. Το Wallstent stent προκάλεσε ήπια φλεγμονώδη αντίδραση και μεταπλασία του ουροθηλίου; Το CEG stent πιο έντονη αντίδραση και τέλος την πίο έντονη φλεγμονώδη αντίδραση προκάλεσε το Passager stent με συνοδό νέκρωση του ουροθηλίου. Τα επικαλλυμένα stents δεν εμφάνισαν ουροθηλιακή υπερπλασία στην έσω επιφάνεια του stent. Τα πειραματικά αποτελέσματα δείχνουν ότι το απλό Wallstent stent προκαλεί λιγότερη φλεγμονώδη αντίδραση των παρακείμενων ιστών σε σύγκριση με τα επικαλλυμένα stents. Απο την αλλη πλευρά τα επικαλυπτόμενα stents περιορίζουν σημaντικά την ουροθηλιακή υπερπλασία αλλα έχουν την τάση να μεταναστεύουν προς την ουροδόχο κύστη. / We report out experience with the use of metallic self expandable and balloon expandable stents for the treatment of malignant ureteral obstruction. We treated 12 consecutive patients with malignant ureteral obstruction, for a total of 14 ureters with stents placed. We placed metallic balloon exspandable stents in 6 patients and self-expandable metallic stents in the remaining 6. mean patient age was 65 years and mean followup was 9 months.(range 8 to 16). Of the ureters 11 were patent without any additional manipulations during the followup of 8 to 16 months. Secondary interventions were needed in 3 cases because of obstructive urothelial hyperplastic reaction,tumor ingrowth and local recurrence of the primary cancer invading the upper end of the stent. Two patients died 2 and 10 months after placement of the stent. Both types of metal stents have advantages and disadvantages that must be balanced against each other when choosing the ideal device for the treatment of obstruction. Implantation of a metal self-expanding or balloon expanding stent is safe and effective for the palliative treatment of malignant ureteral obstruction in late stage cancer patient.

Introdução: Apesar dos avanços significativos no tratamento endovascular das doenças arteriais coronarianas e periféricas, a reestenose intra-stent continua sendo o principal limitante a médio prazo desses procedimentos. O mecanismo da reestenose intra-stent é principalmente a hiperplasia intimal, já que o stent impede a retração elástica aguda e resiste ao remodelamento geométrico negativo tardio. A hiperplasia intimal ocorre basicamente em resposta à formação de trombo local, à inflamação e às dissecções intimais e mediais secundárias à injúria causada pelo stent, sendo o grau de resposta intimal a base dos efeitos a longo prazo. O uso de stents com hastes menores e revestidos com drogas ou polímeros tem sido considerado uma nova alternativa para a prevenção da reestenose intra-stent. Objetivo: Analisar a resposta arterial ao implante de stent de cromo-cobalto sem e com revestimento de polímero Camouflage® em artérias carótidas de suínos, utilizando os seguintes parâmetros histológicos: grau de endotelização, conteúdo de células musculares lisas, grau de angiogênese, conteúdo de fibrina, grau de inflamação e injúria; além da análise histomorfométrica. Método: Stents balões-expansíveis de cromo-cobalto ( 8 stents CC Flex e 5 stents CC Flex Proactive) de 4 x 16 mm foram implantados em artérias carótidas comuns de oito suínos jovens, sendo um stent liberado em cada artéria. Após 30 dias, as artérias contendo os stents foram removidas, fixadas e coradas pelos métodos de hematoxilina/eosina e Verhoeff/Van Giesson. O segmento arterial contendo o stent foi dividido em 3 blocos distintos: proximal, médio e distal. Os cortes histológicos foram obtidos utilizando-se micrótomo de impacto (Polycut S, Leica, Alemanha) equipado com navalha de tungstênio de 16 cm, tipo D (Leica, Alemanha), com 5 ^m de espessura. A navalha de tungstênio mantém as hastes dos stents intactas nas secções transversas, minimizando os artefatos potenciais causados pela retirada dos stents. A avaliação foi realizada através de critérios histológicos e histomorfométricos. Resultados: Todos os stents foram implantados com sucesso e sem dificuldades técnicas. A análise histológica em 30 dias evidenciou alto grau de endotelização em todos os segmentos avaliados e leve à moderada infiltração de células musculares na íntima. Observou-se baixo grau de angiogênese em cerca de 50% dos segmentos avaliados e ausência completa de deposição de fibrina em pelo menos 80%, com distribuição semelhante entre os grupos. A resposta inflamatória e o grau de injúria causadas pelas hastes dos stents também foram discretas e similares entre os grupos e não houve correlação entre resposta inflamatória e injúria e desses parâmetros com a área de neoíntima. O grau de obstrução neo-intimal identificada neste período foi pequeno (15,1% +/- 8,38 CC Flex x 15,5%+/- 5,39 CC Flex ProActive) e estatisticamente não significativo entre os grupos (p=0,785). Conclusão: Os achados deste estudo experimental sugerem que o uso de stents de cromo-cobalto revestidos com polímero Camouflage® em artérias carótidas de suínos parece estar associado, pelo menos no curto prazo, a uma resposta histológica semelhante àquela encontrada após o implante de stents de cromo-cobalto não revestidos. Neste período não se observou uma menor hiperplasia intimal em virtude do revestimento de polímero. / Introduction: Despite all the advances in the endovascular treatment of coronary and peripheral artery diseases, in-stent restenosis is still the main limiting factor of these procedures in the medium and long-term. The mechanism of in-stent restenosis is mainly the intimal hyperplasia, as the stent prevents acute elastic recoil and later negative geometric arterial remodeling. Intimal hyperplasia occurs basically in response to the formation of local thrombus, inflammation and intimal and medial dissections secondary to the injury caused by the stent, with the degree of intimal response being the cause of long-term effects. Coating drug-eluting stents with polymers and drugs with thinner struts have been considered a new alternative for in-stent restenosis prevention. Objective: Analyse the arterial response to the cobalt-chromium stent implant with and without polymer coating Camouflage® in carotid arteries of pigs, using the following histological parameters: degree of endothelialization, smooth muscle cells (SMC) content, degree of angiogenesis, intimal fibrin content, degree of inflammation and injury; plus histomorphometric analysis. Method: Cobaltchromium balloon-expandable stents (8 CC Flex stents and 5 CC Flex Proactive), 4 x 16 mm, were deployed in common carotid arteries of 8 young pigs, with one stent being deployed in each artery. After 30 days, the arteries containing the stents were removed and underwent fixation and staining using the hematoxilin/eosin and Verhoeff /Van Giesson methods. The arterial segment containing the stent was divided into 3 distinct portions: proximal, middle and distal. The histological sections were obtained using impact microtome (Polycut S, Leica, Germany), equipped with a 16 cm, type D, 5 ^m thick tungsten knife (Leica, Germany). The tungsten knife maintains the stent shaft intact in cross sections, minimizing the potential artifacts caused by stent removal. The evaluation was carried out using histological and histomorfometric criteria. Results: All the stents were deployed with success and with no technical difficulties. The histological analysis performed after 30 days showed a high level of endothelialization in all the evaluated portions and mild to moderate infiltration of the SMC in the intima layer. A low level of angiogenesis of about 50% of the evaluated portions was observed and a complete absence of fibrin deposition in at least 80% of the portions, with similar distribution among the groups. The inflammatory response and the level of injury caused by the struts of the stents were also minimum and this was similar among the groups. There was no correlation between inflammatory response and injury and between the two latter parameters and the neo-intima area. The level of neo-intimal obstruction identified in this period was small (15,1% +/- 8,38 CC Flex x 15,5%+/- 5,39 CC Flex ProActive ) and no statistical significance between the groups (p=0,785). Conclusion: The findings of this experimental study suggest the use of balloonexpandable cobalt-chromium stents coated with polymer Camouflage® in carotid arteries of pigs seems to be associated, at least in the short-term, with a similar histological response to that found in the implantation of non-coated cobalt-chromium stents. In this period, a lower intimal hyperplasia was not observed with polymer coating stents.

Introdução: Apesar dos avanços significativos no tratamento endovascular das doenças arteriais coronarianas e periféricas, a reestenose intra-stent continua sendo o principal limitante a médio prazo desses procedimentos. O mecanismo da reestenose intra-stent é principalmente a hiperplasia intimal, já que o stent impede a retração elástica aguda e resiste ao remodelamento geométrico negativo tardio. A hiperplasia intimal ocorre basicamente em resposta à formação de trombo local, à inflamação e às dissecções intimais e mediais secundárias à injúria causada pelo stent, sendo o grau de resposta intimal a base dos efeitos a longo prazo. O uso de stents com hastes menores e revestidos com drogas ou polímeros tem sido considerado uma nova alternativa para a prevenção da reestenose intra-stent. Objetivo: Analisar a resposta arterial ao implante de stent de cromo-cobalto sem e com revestimento de polímero Camouflage® em artérias carótidas de suínos, utilizando os seguintes parâmetros histológicos: grau de endotelização, conteúdo de células musculares lisas, grau de angiogênese, conteúdo de fibrina, grau de inflamação e injúria; além da análise histomorfométrica. Método: Stents balões-expansíveis de cromo-cobalto ( 8 stents CC Flex e 5 stents CC Flex Proactive) de 4 x 16 mm foram implantados em artérias carótidas comuns de oito suínos jovens, sendo um stent liberado em cada artéria. Após 30 dias, as artérias contendo os stents foram removidas, fixadas e coradas pelos métodos de hematoxilina/eosina e Verhoeff/Van Giesson. O segmento arterial contendo o stent foi dividido em 3 blocos distintos: proximal, médio e distal. Os cortes histológicos foram obtidos utilizando-se micrótomo de impacto (Polycut S, Leica, Alemanha) equipado com navalha de tungstênio de 16 cm, tipo D (Leica, Alemanha), com 5 ^m de espessura. A navalha de tungstênio mantém as hastes dos stents intactas nas secções transversas, minimizando os artefatos potenciais causados pela retirada dos stents. A avaliação foi realizada através de critérios histológicos e histomorfométricos. Resultados: Todos os stents foram implantados com sucesso e sem dificuldades técnicas. A análise histológica em 30 dias evidenciou alto grau de endotelização em todos os segmentos avaliados e leve à moderada infiltração de células musculares na íntima. Observou-se baixo grau de angiogênese em cerca de 50% dos segmentos avaliados e ausência completa de deposição de fibrina em pelo menos 80%, com distribuição semelhante entre os grupos. A resposta inflamatória e o grau de injúria causadas pelas hastes dos stents também foram discretas e similares entre os grupos e não houve correlação entre resposta inflamatória e injúria e desses parâmetros com a área de neoíntima. O grau de obstrução neo-intimal identificada neste período foi pequeno (15,1% +/- 8,38 CC Flex x 15,5%+/- 5,39 CC Flex ProActive) e estatisticamente não significativo entre os grupos (p=0,785). Conclusão: Os achados deste estudo experimental sugerem que o uso de stents de cromo-cobalto revestidos com polímero Camouflage® em artérias carótidas de suínos parece estar associado, pelo menos no curto prazo, a uma resposta histológica semelhante àquela encontrada após o implante de stents de cromo-cobalto não revestidos. Neste período não se observou uma menor hiperplasia intimal em virtude do revestimento de polímero. / Introduction: Despite all the advances in the endovascular treatment of coronary and peripheral artery diseases, in-stent restenosis is still the main limiting factor of these procedures in the medium and long-term. The mechanism of in-stent restenosis is mainly the intimal hyperplasia, as the stent prevents acute elastic recoil and later negative geometric arterial remodeling. Intimal hyperplasia occurs basically in response to the formation of local thrombus, inflammation and intimal and medial dissections secondary to the injury caused by the stent, with the degree of intimal response being the cause of long-term effects. Coating drug-eluting stents with polymers and drugs with thinner struts have been considered a new alternative for in-stent restenosis prevention. Objective: Analyse the arterial response to the cobalt-chromium stent implant with and without polymer coating Camouflage® in carotid arteries of pigs, using the following histological parameters: degree of endothelialization, smooth muscle cells (SMC) content, degree of angiogenesis, intimal fibrin content, degree of inflammation and injury; plus histomorphometric analysis. Method: Cobaltchromium balloon-expandable stents (8 CC Flex stents and 5 CC Flex Proactive), 4 x 16 mm, were deployed in common carotid arteries of 8 young pigs, with one stent being deployed in each artery. After 30 days, the arteries containing the stents were removed and underwent fixation and staining using the hematoxilin/eosin and Verhoeff /Van Giesson methods. The arterial segment containing the stent was divided into 3 distinct portions: proximal, middle and distal. The histological sections were obtained using impact microtome (Polycut S, Leica, Germany), equipped with a 16 cm, type D, 5 ^m thick tungsten knife (Leica, Germany). The tungsten knife maintains the stent shaft intact in cross sections, minimizing the potential artifacts caused by stent removal. The evaluation was carried out using histological and histomorfometric criteria. Results: All the stents were deployed with success and with no technical difficulties. The histological analysis performed after 30 days showed a high level of endothelialization in all the evaluated portions and mild to moderate infiltration of the SMC in the intima layer. A low level of angiogenesis of about 50% of the evaluated portions was observed and a complete absence of fibrin deposition in at least 80% of the portions, with similar distribution among the groups. The inflammatory response and the level of injury caused by the struts of the stents were also minimum and this was similar among the groups. There was no correlation between inflammatory response and injury and between the two latter parameters and the neo-intima area. The level of neo-intimal obstruction identified in this period was small (15,1% +/- 8,38 CC Flex x 15,5%+/- 5,39 CC Flex ProActive ) and no statistical significance between the groups (p=0,785). Conclusion: The findings of this experimental study suggest the use of balloonexpandable cobalt-chromium stents coated with polymer Camouflage® in carotid arteries of pigs seems to be associated, at least in the short-term, with a similar histological response to that found in the implantation of non-coated cobalt-chromium stents. In this period, a lower intimal hyperplasia was not observed with polymer coating stents.