Introdução: A utilização da técnica endovascular para tratar as diversas afecções da aorta têm suplantado as técnicas abertas tradicionais, sendo particularmente promissora no trauma 1. A ruptura traumática da aorta é a segunda causa de morte por acidente de trânsito 2,3; e o reparo endoluminal dessas lesões com endopróteses apresenta menor taxa de mortalidade e paraplegia quando comparada a cirurgia aberta, no entanto os resultados a longo prazo ainda não estão disponíveis2-7. As próteses aprovadas e comercialmente disponíveis, até o momento desse estudo, foram desenhadas para doença aneurismática, com diâmetro muito superior ao diâmetro da aorta de jovens (vítimas de trauma). Esse sobredimensionamento (oversizing) pode levar a alteração mecânica na interação da prótese com a parede aórtica, comprometendo a vascularização e aumento o risco de complicações relacionadas ao implante de endopróteses 8-12. Objetivos: Analisar, a partir de um modelo animal experimental, o efeito biomecânico e histopatológico de quatro níveis diferentes de sobredimensionamento de endopróteses sobre a aorta não aterosclerótica, semelhante às encontradas em pacientes jovens vítimas de trauma. Método: O diâmetro da aorta torácica suína é semelhante ao da aorta de jovens adultos (18-20 mm), desta forma 25 porcos foram randomizados em 5 grupos: 1 controle (sem stent) e 4 grupos de sobredimensionamento (A: 10% -19 %, B: 20% -29%, C: 30% -39%, e D: >40% de sobredimensionamento). Dois tipos de testes biomecânicos foram realizados em todas as aortas 4 semanas após a implantação da endoprótese: \" z\" endoprótese; e o teste de biomecânica propriamente dito dos fragmentos aórticos coletados. Os fragmentos foram, então, submetidos a uma análise histológica e imunohistoquímica. Resultados: Os resultados do teste de destacamento, que avaliou a força necessária para remover o stent da aorta, foram semelhantes nos quatro grupos (A: 42 N, B: 41 N, C: 46 N e D: 46 N, p= 0,881204). O segundo teste foi realizado em três segmentos da aorta. Força máxima, estresse máximo e tensão máxima suportada pela parede da aorta tiveram uma correlação negativa e linear com o oversizing, isto é, quanto maior o oversizing, menor a resistência do fragmento à ruptura. Houve diferenças significativas em todos os quatro grupos, quando comparados com o grupo controle. A deformação máxima e o Strain, que refletem as propriedades elásticas da parede da aorta, foram muito semelhantes em todos os quatro grupos de sobredimensionamento. Mas, uma diminuição significativa da elasticidade foi encontrada quando comparados cada um dos grupos com o grupo controle (p= 0,0000001). A análise histológica e imunohistoquímica demonstrou que a parede da aorta tem uma perda significativa de fibras musculares e ?-actina com o aumento do sobredimensionamento (p= 0,000198 e p= 0,002031, respectivamente). A quantidade de fibra elástica apresentou uma queda significativa independente do sobredimensionamento (p= 0,0000001). Conclusões: Os quatro níveis de sobredimensionamento estudados não demonstraram diferenças significativas no teste de destacamento. Os testes biomecânicos dos fragmentos da aorta mostraram uma diminuição na resistência da parede aórtica proporcional ao aumento do oversizing. A elasticidade da parede aórtica sofre alteração significativa independente do sobredimensionamento utilizado. Os exames histopatológicos e imunohistoquímicos comprovaram o desarranjo na estrutura da parede aórtica com a utilização de endopróteses, resultando na diminuição da quantidade de fibras elásticas e musculares / Introduction: The use of endovascular techniques to treat the various disorders of the aorta has supplanted traditional open techniques, and is particularly promising in trauma1. The traumatic rupture of the aorta is the second leading cause of death by traffic accident2, 3, and repair of these lesions with endoluminal stents has showed lower mortality and paraplegia when compared to open surgery, however the long-term results are not yet available2-7. The endoprosthesis approved and commercially available during this study were designed to aneurysmal disease, with a diameter greater than the diameter of the aorta of young people ( ) \" z \" prosthesis with the aortic wall, affecting the vascularization and raising the risk of complications related to stent-graft implantation8-12. Purpose: Analyze, from an experimental animal model, the biomechanical and histological effects of four different levels of stents-graft oversizing in non-atherosclerotic aortas; such as those aorta found in young individuals who undergo stent-graft repair for traumatic aortic injuries. Methods: The diameter of the porcine thoracic aorta is similar to the aorta of young adults (18-20 mm), so 25 pigs were randomized into 5 groups: 1 control (without stent-graft) and 4 oversizing groups (A: 10%-19%, B: 20%-29%, C: 30%-39%, and D: .40%). Two types of biomechanical tests were performed on all aortas 4 weeks after endoprosthesis deployment: The \"detachment\" of the stent, and the biomechanics test of aortic fragments collected. The fragments were submitted to a histological and an immunohistochemistry analysis. Results: The results of the detachment test, which analyzed the strength necessary to remove the stent-graft from the aorta, were similar in the 4 groups (A: 42 N, B: 41 N, C: 46 N e D: 46 N, p= 0,881204). The second test was performed in 3 aortic segments. Maximum strength, maximum stress, and maximum tension supported by the aortic wall had a negative and linear correlation with oversizing. There were significant differences in all 4 groups when compared with the control group. The maximum deformation and strain, which reflect the elastic properties of the aortic wall, were very similar in all 4 groups. But a significant decrease in elasticity was found when compared each group with the control group (p = 0.0000001). Histological and immunohistochemistry analysis supported that the aortic wall has a signifi-?-actin by increasing the oversize (p = 0.000198 p = 0.002031, respectively). The amount of elastic fiber showed a significant drop regardless of the oversizing (p = 0.0000001). Conclusion: The four levels of oversizing studied did not show significant differences in the detachment test. Biomechanical tests of the fragments of the aorta showed a decrease in resistance of the aortic wall with increase in oversize. The elasticity of the aortic wall undergoes significant change independent of the oversizing used. The histopathological and immunohistochemical examinations confirmed the breakdown in the structure of the aortic wall with the use of stents-graft, resulting in decreased amount of elastic and muscle fibers.

Introdução: A utilização da técnica endovascular para tratar as diversas afecções da aorta têm suplantado as técnicas abertas tradicionais, sendo particularmente promissora no trauma 1. A ruptura traumática da aorta é a segunda causa de morte por acidente de trânsito 2,3; e o reparo endoluminal dessas lesões com endopróteses apresenta menor taxa de mortalidade e paraplegia quando comparada a cirurgia aberta, no entanto os resultados a longo prazo ainda não estão disponíveis2-7. As próteses aprovadas e comercialmente disponíveis, até o momento desse estudo, foram desenhadas para doença aneurismática, com diâmetro muito superior ao diâmetro da aorta de jovens (vítimas de trauma). Esse sobredimensionamento (oversizing) pode levar a alteração mecânica na interação da prótese com a parede aórtica, comprometendo a vascularização e aumento o risco de complicações relacionadas ao implante de endopróteses 8-12. Objetivos: Analisar, a partir de um modelo animal experimental, o efeito biomecânico e histopatológico de quatro níveis diferentes de sobredimensionamento de endopróteses sobre a aorta não aterosclerótica, semelhante às encontradas em pacientes jovens vítimas de trauma. Método: O diâmetro da aorta torácica suína é semelhante ao da aorta de jovens adultos (18-20 mm), desta forma 25 porcos foram randomizados em 5 grupos: 1 controle (sem stent) e 4 grupos de sobredimensionamento (A: 10% -19 %, B: 20% -29%, C: 30% -39%, e D: >40% de sobredimensionamento). Dois tipos de testes biomecânicos foram realizados em todas as aortas 4 semanas após a implantação da endoprótese: \" z\" endoprótese; e o teste de biomecânica propriamente dito dos fragmentos aórticos coletados. Os fragmentos foram, então, submetidos a uma análise histológica e imunohistoquímica. Resultados: Os resultados do teste de destacamento, que avaliou a força necessária para remover o stent da aorta, foram semelhantes nos quatro grupos (A: 42 N, B: 41 N, C: 46 N e D: 46 N, p= 0,881204). O segundo teste foi realizado em três segmentos da aorta. Força máxima, estresse máximo e tensão máxima suportada pela parede da aorta tiveram uma correlação negativa e linear com o oversizing, isto é, quanto maior o oversizing, menor a resistência do fragmento à ruptura. Houve diferenças significativas em todos os quatro grupos, quando comparados com o grupo controle. A deformação máxima e o Strain, que refletem as propriedades elásticas da parede da aorta, foram muito semelhantes em todos os quatro grupos de sobredimensionamento. Mas, uma diminuição significativa da elasticidade foi encontrada quando comparados cada um dos grupos com o grupo controle (p= 0,0000001). A análise histológica e imunohistoquímica demonstrou que a parede da aorta tem uma perda significativa de fibras musculares e ?-actina com o aumento do sobredimensionamento (p= 0,000198 e p= 0,002031, respectivamente). A quantidade de fibra elástica apresentou uma queda significativa independente do sobredimensionamento (p= 0,0000001). Conclusões: Os quatro níveis de sobredimensionamento estudados não demonstraram diferenças significativas no teste de destacamento. Os testes biomecânicos dos fragmentos da aorta mostraram uma diminuição na resistência da parede aórtica proporcional ao aumento do oversizing. A elasticidade da parede aórtica sofre alteração significativa independente do sobredimensionamento utilizado. Os exames histopatológicos e imunohistoquímicos comprovaram o desarranjo na estrutura da parede aórtica com a utilização de endopróteses, resultando na diminuição da quantidade de fibras elásticas e musculares / Introduction: The use of endovascular techniques to treat the various disorders of the aorta has supplanted traditional open techniques, and is particularly promising in trauma1. The traumatic rupture of the aorta is the second leading cause of death by traffic accident2, 3, and repair of these lesions with endoluminal stents has showed lower mortality and paraplegia when compared to open surgery, however the long-term results are not yet available2-7. The endoprosthesis approved and commercially available during this study were designed to aneurysmal disease, with a diameter greater than the diameter of the aorta of young people ( ) \" z \" prosthesis with the aortic wall, affecting the vascularization and raising the risk of complications related to stent-graft implantation8-12. Purpose: Analyze, from an experimental animal model, the biomechanical and histological effects of four different levels of stents-graft oversizing in non-atherosclerotic aortas; such as those aorta found in young individuals who undergo stent-graft repair for traumatic aortic injuries. Methods: The diameter of the porcine thoracic aorta is similar to the aorta of young adults (18-20 mm), so 25 pigs were randomized into 5 groups: 1 control (without stent-graft) and 4 oversizing groups (A: 10%-19%, B: 20%-29%, C: 30%-39%, and D: .40%). Two types of biomechanical tests were performed on all aortas 4 weeks after endoprosthesis deployment: The \"detachment\" of the stent, and the biomechanics test of aortic fragments collected. The fragments were submitted to a histological and an immunohistochemistry analysis. Results: The results of the detachment test, which analyzed the strength necessary to remove the stent-graft from the aorta, were similar in the 4 groups (A: 42 N, B: 41 N, C: 46 N e D: 46 N, p= 0,881204). The second test was performed in 3 aortic segments. Maximum strength, maximum stress, and maximum tension supported by the aortic wall had a negative and linear correlation with oversizing. There were significant differences in all 4 groups when compared with the control group. The maximum deformation and strain, which reflect the elastic properties of the aortic wall, were very similar in all 4 groups. But a significant decrease in elasticity was found when compared each group with the control group (p = 0.0000001). Histological and immunohistochemistry analysis supported that the aortic wall has a signifi-?-actin by increasing the oversize (p = 0.000198 p = 0.002031, respectively). The amount of elastic fiber showed a significant drop regardless of the oversizing (p = 0.0000001). Conclusion: The four levels of oversizing studied did not show significant differences in the detachment test. Biomechanical tests of the fragments of the aorta showed a decrease in resistance of the aortic wall with increase in oversize. The elasticity of the aortic wall undergoes significant change independent of the oversizing used. The histopathological and immunohistochemical examinations confirmed the breakdown in the structure of the aortic wall with the use of stents-graft, resulting in decreased amount of elastic and muscle fibers.

Univerzita Karlova v Praze 1. lékařská fakulta Autoreferát disertační práce Optimalizace indikací chirurgického a endovaskulárního ošetření intrakraniálních aneurysmat Anna Štekláčová 2018 2 Doktorské studijní programy v biomedicíně Univerzita Karlova v Praze a Akademie věd České republiky Obor: Neurovědy Předseda oborové rady: Prof. MUDr. Karel Šonka, DrSc. Školicí pracoviště: Neurochirurgická a neuroonkologická klinika 1. LF UK a ÚVN, Praha Školitel: Prof. MUDr. Vladimír Beneš, DrSc. Disertační práce bude nejméně pět pracovních dnů před konáním obhajoby zveřejněna k nahlížení veřejnosti v tištěné podobě na Oddělení pro vědeckou činnost a zahraniční styky Děkanátu 1. lékařské fakulty. 3 Obsah Abstrakt - Česky ..................................................................................... 4 Abstract - English ................................................................................... 5 Úvod........................................................................................................ 6 Hypotézy a cíle studie............................................................................. 6 Materiál a metody ................................................................................... 7 Výsledky...

Η οπτική συνεκτική τομογραφία με τη χρήση συχνοτήτων ( FD-OCT) είναι μια ενδαγγειακή απεικονιστική μέθοδος που χρησιμοποιεί εγγύς στο υπέρυθρο φως, για να παράγει υψηλής ανάλυσης εικόνες του τοιχώματος του αυλού του αγγείου. Όπως και στην τεχνολογία υπερήχων, εκπέμπεται φωτεινή ενέργεια η οποία ανακλάται και εξασθενεί, σύμφωνα με την υφή του προσπιπτομένου ιστού. Το OCT μπορεί να απεικονίσει, με ανάλυση από 10 έως 20 μm, μικροδομές του αγγειακού τοιχώματος με εξαίσια λεπτομέρεια. Μέχρι σήμερα, η δυνατότητα εφαρμογής της μεθόδου είχε περιοριστεί σε μικρές αρτηρίες διαμέτρου έως 4mm και δεν είχε εφαρμοστεί in vivo στα αγγεία των κάτω άκρων, κάτωθεν του επιπέδου των βουβώνων. Σκοπός της παρούσας μελέτης είναι να αναφερθεί για παγκοσμίως πρώτη φορά η ασφάλεια και η σκοπιμότητα της απεικόνισης με Οπτική Συνεκτική Τομογραφία του αρτηριακού άξονα των κάτω άκρων , κάτωθεν του επιπέδου της βουβώνας ( μηροϊγνυακός άξονας και κνημιαία αγγεία), καθώς και οι σχετιζόμενες με το FD-OCT επιπλοκές. Επιπρόσθετα, να διερευνηθούν για πρώτη φορά, με τη χρήση FD-OCT, τα χαρακτηριστικά του αγγειακού τοιχώματος του ανωτέρω άξονα (τόσο πριν όσο και μετά από αγγειοπλαστική ή/και τοποθέτηση stent), η μορφολογία της αθηρωματικής πλάκας, η μορφολογία και η ποσοτικοποίηση της υπερπλασίας του νέου εσωτερικού χιτώνα (neointima) εντός του stent, η επαναστένωση εντός του stent (ISR) και η κακή εναπόθεση (malapposition) των stent struts σε μια σειρά από ασθενείς που πάσχουν από περιφερική αρτηριοπάθεια (PAD). Μελετήθηκαν, με ποσοτική ανάλυση του αυλού τους (Quantitative vascular analysis), αρτηρίες με διάμετρο έως 7 χιλιοστά. Μικτά χαρακτηριστικά από περιοχές πλούσιες σε λιπίδια, εναποθέσεις ασβεστίου και ασβεστοποιημένες πλάκες, νεκρωτικές περιοχές και ίνωση εντοπίστηκαν σε όλες τις απεικονιζόμενες αθηροσκληρωτικές βλάβες. Ωστόσο, με βάση το επικρατέστερο από τα παραπάνω απεικονιστικά χαρακτηριστικά, οι βλάβες στο πλαίσιο της έρευνας ταξινομήθηκαν ως αμιγώς ινωτικές, ως ινοασβεστοποιημένες, ως πλούσιες σε λιπίδια και τέλος ως νεκρωτικές/ασβεστοποιημένες. Συσσώρευση των μακροφάγων εντός της αθηρωματικής πλάκας σημειώθηκε σε μικρό ποσοστό των de novo αθηρωματικών αλλοιώσεων. Ποικίλοι βαθμοί υπερπλασίας του νέου έσω χιτώνα απεικονίσθηκαν σε όλες τις περιπτώσεις ISR αλλοιώσεων, με καθαρά ινωτικά χαρακτηριστικά και σημαντική νεοαγγείωση σε κάποιες από αυτές. Η νεοαγγείωση συνέπεσε με το επίπεδο της μέγιστης στένωσης του αγγειακού αυλού. Σημαντικού βαθμού διαχωρισμός με μεγάλο περιορισμό του αγγειακού αυλού, τέτοιος ώστε να απαιτηθεί να τοποθετηθεί ενδοαυλικό stent, ανιχνεύθηκε σε αρκετές περιπτώσεις της de novo αθηρωμάτωσης. Η ψηφιακή αφαιρετική αγγειογραφία παρέλειψε να προσδιορίσει μεγάλο ποσοστό των σοβαρών διαχωρισμών μετά από αγγειοπλαστική. Η νεοαθηροσκλήρυνση εντός του νέου έσω χιτώνα των κνημιαίων φαρμακευτικών stents (DES), είναι ένα συχνό εύρημα τόσο στους συμπτωματικούς όσο και στους ασυμπτωματικούς ασθενείς. Μπορούμε να υποθέσουμε ότι, κατά αναλογία με τα εμφυτευμένα DES στα στεφανιαία αγγεία, η ελαττωματική ενδοθηλιοποίηση που προκαλείται από την εκλυόμενη φαρμακευτική ουσία, μαζί με την νεοαγγείωση που αναπτύσσεται μεταξύ των stent struts, μπορούν να υποδαυλίσουν την νεοαθηροσκλήρυνση εντός του νέου έσω χιτώνα των κνημιαίων DES, η οποία μπορεί να οδηγήσει σε επαναστένωση εντός του stent (ISR) και απώλεια του εμβαδού του αυλού των περιφερικών αρτηριών. Οι παρατηρήσεις της μελέτης αυτής θέτουν σε αμφισβήτηση το παραδοσιακό τρόπο κατανόησης της περιφερειακής επαναστένωσης εντός του stent ως μιας απλής υπερπολλαπλασιαστικής απάντησης στο βαρότραυμα. Η απεικόνιση με FD-OCT είναι ένα βέλτιστο πειραματικό εργαλείο για την αξιολόγηση της εξέλιξης της αθηροσκληρωματικής νόσου και την επαναστένωση του αγγείου. Μπορεί να παρέχει υψηλής ευκρίνειας ενδοαγγειακή απεικόνιση κατά τη διάρκεια αγγειοπλαστικών επεμβάσεων στα κάτω άκρα και θα μπορούσε να αποδειχθεί κλινικά χρήσιμο για τον προσδιορισμό της εντός του stent πρόπτωσης ιστού και του strut malapposition. Παρ 'όλα αυτά, δεν πρέπει να χρησιμοποιηθεί ως εργαλείο για τη συνήθη κλινική πρακτική μέχρι να προκύψουν στοιχεία από περαιτέρω κλινικές δοκιμές για τον καθορισμό των ειδικών ενδείξεων της απεικόνισης με FD-OCT στις περιφερικές αρτηρίες. / Optical coherence tomography (OCT) is a catheter-based imaging method that employs near-infrared light to produce high-resolution intravascular images. OCT can readily visualize vessel microstructure at a 10- to 20-μm resolution with exquisite detail. To date, however, applicability of the method has been limited to small diameter arteries (≤4 mm). To the best of the author’s knowledge, this study is the first worldwide that demonstrates the safety and clinical feasibility of frequency domain Optical Coherence Tomography (FD-OCT) imaging of infrainguinal vessels in vivo during infrainguinal angioplasty procedures. It is also the first study that reports the use of intravascular FD-OCT to detect and characterize in-stent neointimal tissue following infrapopliteal drug eluting stent (DES) placement in patients suffering from critical limb ischemia. Quantitative lumen analysis of arteries with diameter up to 7 mm was performed. High-resolution OCT images provided exquisite two-dimensional axial and longitudinal views of the infrainguinal arteries and allowed thorough investigation of a variety of angioplasty sequela, including and not limited to intimal tears and dissection flaps, white and red thrombus, stent mesh malapposition, and intrastent plaque prolapse. Of interest, OCT identified cases of suboptimal postangioplasty outcome that single-plane subtraction angiography did not recognize and accounted. Mixed features of lipid pool areas, calcium deposits and calcified plaques, necrotic areas, and fibrosis were identified in all of the imaged atherosclerotic lesions. However, based on the predominant baseline imaging findings, lesions under investigation were classified as purely fibrotic, fibrocalcific, mostly lipid-laden and necrotic/calcified. Intraplaque accumulation of macrophages was noted in some of de novo atheromatic lesions. Varying degrees of neointimal hyperplasia were demonstrated in all cases of in stent restenosis (ISR) lesions with purely fibrotic features and considerable neovascularization in some of them. The latter finding coincided with the level of maximum vessel stenosis in all cases. Neoatherosclerosis following infrapopliteal DES placement is a frequent finding in both symptomatic and asymptomatic patients. Our preliminary observations allow us to speculate that analogous to coronary implanted DES, defective endothelialization induced by the eluted drug, along with neovascularization developing between the stent struts, may incite neointimal neoatherosclerosis, which may result in ISR and lumen loss of the peripheral arteries. It also seems that infrapopliteal neoatherosclerosis may be a significant contributing factor for ISR rather than a minor and sporadic process, highlighting the clinical significance of the phenomenon. Our observations put in dispute the traditional way of understanding peripheral in-stent restenosis as a simple hyperproliferative response to barotraumas and may explain the paramount importance of aggressive risk factor modification strategies. Neointimal neoatherosclerosis as identified by FD-OCT may have a role in the development of below-the-knee restenosis and thus warrants further investigation by larger controlled studies. Moreover, it may prove clinically useful for the determination of intrastent tissue prolapse and strut malapposition. FD-OCT should not be utilized as a tool for routine clinical practice until evidence from further clinical trials emerge to determine the specific indications for OCT imaging of the peripheral arteries.