Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-09-25T21:01:36Z No. of bitstreams: 2 Lais Moraes de Oliveira - 2012 - dissertação.pdf: 1880277 bytes, checksum: e1834355b94c2185f2db85cc1b9d7023 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-09-26T11:58:07Z (GMT) No. of bitstreams: 2 Lais Moraes de Oliveira - 2012 - dissertação.pdf: 1880277 bytes, checksum: e1834355b94c2185f2db85cc1b9d7023 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-26T11:58:07Z (GMT). No. of bitstreams: 2 Lais Moraes de Oliveira - 2012 - dissertação.pdf: 1880277 bytes, checksum: e1834355b94c2185f2db85cc1b9d7023 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-07-17 / Caryocar brasiliense Camb. (“pequi”) is a native plant from the Cerrado region of Brazil that contains several bioactive components. Data from literature has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. In this work, we evaluated the vasorelaxant effect of the crude hydroalcoholic extract (CHE) of C. brasiliense leaves, and its organic fractions (hexane (HF), chloroform (CF), ethyl acetate (AEF), butanol (BF)), in the rat thoracic aorta. We found that CHE completely relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, while butanolic fraction (BF) produced an effect similar to that of the CHE. Induced aortic relaxation BF by was abolished by endothelium removal, by incubation with the nitric oxide synthase inhibitor (L-NAME), and the soluble guanylate cyclase inhibitor (ODQ). However, incubation with either atropine (a muscarinic receptor antagonist) or pyrilamine (a histamine H1-receptor antagonist) had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin (a cyclooxygenase inhibitor) and tetraethylammonium (a non-selective K+ channel blocker). The vasorelaxation induced by BF in endothelium-intact aortic rings precontracted with KCl was reduced after incubation with L-NAME. Taken together, the results reveal that C. brasiliense possesses in vitro vasorelaxant effect in rat thoracic aorta and this effect involves stimulation of the nitric oxide/cyclic GMP pathway. / Caryocar brasiliense Camb. (“pequi”) é uma planta nativa do Cerrado Brasileiro que apresenta diversos componentes bioativos. Dados da literatura demonstraram que a suplementação dietética à base de pequi diminuiu a pressão arterial de atletas voluntários. Neste trabalho, avaliou-se o efeito vasorelaxante do extrato bruto hidroalcoólico (EBH) das folhas de C. brasiliense e de suas frações orgânicas (hexânica (FH), clorofórmica (FC), acetato de etila (FAE), butanólica (FB)) em preparações de aorta torácica de ratos. O EBH relaxou, de modo concentraçãodependente, anéis de aorta torácica pré-contraídos com fenilefrina, sendo que a FB promoveu efeito semelhante ao observado com o EBH. O relaxamento aórtico induzido pela FB foi abolido pela remoção do endotélio vascular, pela incubação prévia do inibidor da sintase de óxido nítrico (L-NAME) e pelo inibidor da guanilato ciclase (ODQ). Entretanto, a incubação das preparações aórticas com atropina (antagonista muscarínico) e pirilamina (antagonista histaminérgico H1) não inibiu o vasorelaxamento induzido pela FB. Este efeito também não foi inibido pela indometacina (inibidor da ciclooxigenase) ou pelo tetraetilamônio (bloqueador não seletivo de canais de potássio). O efeito vasorelaxante da FB, em anéis aórticos com endotélio e pré-contraídos com KCl, foi reduzido após a incubação com L-NAME. Conjuntamente, os resultados demonstram que o efeito vasorelaxante in vitro de C. brasiliense em aorta torácica de ratos envolve a estimulação da via do óxido nítrico/GMP cíclico.

<p>The obligate intracellular bacterium <i>Chlamydia pneumoniae (Cp</i>), a common human pathogen, has been associated with atherosclerotic cardiovascular disease. The aetiology of non-rheumatic aortic valve sclerosis has, however, not been clarified. In two prospective studies of 42 and 46 patients undergoing surgical valve replacement because of aortic valve stenosis, the presence of <i>Cp </i>DNA could be demonstrated by polymerase chain reaction (PCR) in 49% and 35% of the sclerotic valves as compared to 9 % and 0%, respectively, of valves from forensic control cases with no heart valve disease. Some inflammatory and infectious diseases are associated with trace element changes. Eleven of 15 trace elements showed changed concentrations in sclerotic valve tissue compared to control valves in support of an active process in the sclerotic valves. Notable was an increased iron concentration in the patients´ valves suggesting a possible link to <i>Cp</i>. Furthermore, a disturbed trace element balance existed in the patients´ sera, the pattern of which was compatible with ongoing infection. In a prospective study of 38 patients operated on for thoracic aortic aneurysm or dissection, <i>Cp</i> DNA <i>w</i>as detected byPCR in 12 % of the aneurysms and the result was confirmed byelectron microscopy(EM<i>).</i> In none of the dissection patients could <i>Cp </i>be demonstratedin the removed tissues. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values for doxycycline and azithromycin increased with longer <i>Cp </i>preincubation times when tested in vitro<i>.</i> EMwas performed to visualise the inactivation at a cellular level.Thus, the results demonstrate <i>Cp </i>in the tissues in non-rheumatic aortic valve sclerosis and in thoracic aortic aneurysm but not in aortic dissection.</p>

The obligate intracellular bacterium Chlamydia pneumoniae (Cp), a common human pathogen, has been associated with atherosclerotic cardiovascular disease. The aetiology of non-rheumatic aortic valve sclerosis has, however, not been clarified. In two prospective studies of 42 and 46 patients undergoing surgical valve replacement because of aortic valve stenosis, the presence of Cp DNA could be demonstrated by polymerase chain reaction (PCR) in 49% and 35% of the sclerotic valves as compared to 9 % and 0%, respectively, of valves from forensic control cases with no heart valve disease. Some inflammatory and infectious diseases are associated with trace element changes. Eleven of 15 trace elements showed changed concentrations in sclerotic valve tissue compared to control valves in support of an active process in the sclerotic valves. Notable was an increased iron concentration in the patients´ valves suggesting a possible link to Cp. Furthermore, a disturbed trace element balance existed in the patients´ sera, the pattern of which was compatible with ongoing infection. In a prospective study of 38 patients operated on for thoracic aortic aneurysm or dissection, Cp DNA was detected byPCR in 12 % of the aneurysms and the result was confirmed byelectron microscopy(EM). In none of the dissection patients could Cp be demonstratedin the removed tissues. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values for doxycycline and azithromycin increased with longer Cp preincubation times when tested in vitro. EMwas performed to visualise the inactivation at a cellular level.Thus, the results demonstrate Cp in the tissues in non-rheumatic aortic valve sclerosis and in thoracic aortic aneurysm but not in aortic dissection.

INTRODUÇÃO: O tratamento endovascular das doenças da aorta é modalidade consagrada atualmente, sendo realizado em indivíduos jovens e idosos, tanto na aorta torácica quanto na abdominal. Esta terapia baseia-se numa interação adequada entre a endoprótese e a parede aórtica. Neste sentido, o conhecimento do comportamento biomecânico da aorta é fundamental. A aorta humana é uma estrutura complexa, com comportamento biomecânico diferente de acordo com a idade, a região e a presença de doenças. Estudos com biomecânica da aorta humana não aneurismática são escassos. OBJETIVOS: Analisar os parâmetros biomecânicos de falência e as características histológicas da aorta torácica e abdominal humana, correlacionando-os com idade e gênero. MÉTODO: Testes destrutivos uniaxiais de espécimes removidos de 26 aortas frescas de cadáveres foram realizados num aparelho de tração universal. Os parâmetros biomecânicos de falência avaliados foram: força, tensão, estresse, deformação e energia de deformação. Foi realizado estudo histológico do tecido aórtico para quantificação de fibras colágenas, musculares e elásticas. RESULTADOS: Foram analisados os testes biomecânicos válidos de 153 espécimes, sendo 95 da aorta torácica e 58 da aorta abdominal. Na comparação entre aorta torácica e abdominal, realizada por análise de variância, foi observado que diâmetro (30,45 versus 23,99 mm; p < 0,001), espessura (1,69 versus 1,44 mm; p < 0,001), força máxima (6,18 versus 4,85 N; p = 0,001), tensão de falência (19,88 versus 14,53 N/cm; p = 0,001), deformação de falência (0,66 versus 0,49; p = 0,003) e a percentagem de fibras elásticas (19,39 versus 14,06 %; p = 0,011) foram maiores, com significância, na aorta torácica. As correlações de Spearman entre idade e força máxima, estresse de falência, tensão de falência, deformação de falência e energia de deformação foram negativas e significativas na aorta torácica e abdominal. As aortas do sexo masculino, através do teste t de Student, apresentaram maior força máxima e tensão de falência. Não houve diferença na composição histológica entre os gêneros. CONCLUSÕES: A aorta torácica é mais resistente e elástica que a aorta abdominal. O conteúdo de fibras elásticas é maior na aorta torácica. Os idosos apresentam aortas menos resistentes e mais rígidas que os jovens. A aorta do sexo masculino é mais resistente / INTRODUCTION: The endovascular repair of aortic diseases is currently widely performed among young and elderly patients, in both the thoracic and abdominal aorta. This treatment is based on an appropriate interaction between the stent graft and the aortic wall. Thus, it is essential to understand the biomechanical behavior of the aorta. The human aorta is a complex vessel with different biomechanical behaviors according to age, location and diseases. There are few biomechanical studies of the human nonaneurysmal aorta. OBJECTIVES: To analyze the biomechanical properties and histological composition of the human aorta according to age and gender. METHODS: Twenty-six human aortas were harvested whole from fresh cadavers during their autopsies. Each aorta was cut into strips for mechanical testing. Uniaxial tensile tests were performed on a tensile-testing machine. The failure load, failure stress, failure tension, failure strain and strain energy were calculated. A histological study was performed to measure the amount of collagen, elastin and smooth muscle cells in the aortic wall. RESULTS: A total of 153 strips were studied (95 from the thoracic aorta and 58 from the abdominal aorta). The diameter (30.45 versus 23.99 mm; p < 0.001), thickness (1.69 versus 1.44 mm; p < 0.001), failure load (6.18 versus 4.85 N; p = 0.001), failure tension (19.88 versus 14.53 N/cm; p = 0.001), failure strain (0.66 versus 0.49; p = 0.003) and elastin amount (19.39 versus 14.06 %; p = 0.011) were all significantly higher for the thoracic aorta than for the abdominal aorta. There was a significant negative Spearman\'s correlation between age and failure load, failure stress, failure tension, failure strain and strain energy. Male aortas had a higher failure load and failure tension than female aortas. No difference in the histological composition was found between the genders. CONCLUSIONS: The thoracic aorta has a higher strength and elasticity than the abdominal aorta. The elastin amount is higher in the thoracic aorta than in the abdominal aorta. The elderly have weaker and stiffer aortas than the young. Male aortas have a higher strength than female aortas

Objectifs : caractériser (1) la morphométrie de la crosse afin d’examiner les critères favorisant les complications et la faisabilité d’endoprothèses (EP) standards. (2) les propriétés mécaniques de l’aorte ascendante (AA) chez le porc, homme sain et en cas de dissection aortique (DAo).Matériels et méthodes :Caractérisation morphométrique : A partir d’angioscanner aortiques les paramètres: (1) morphométriques élémentaires (2) géométriques ; (3) troncs supra-aortiques (TSAo), sont mesurésCaractérisation mécanique : In vivo : à partir de données échographiques et hémodynamiques, les paramètres élastiques sont calculés.In vitro : tests de traction bi-axiale sur l’AA plus une analyse histomorphométrique et microstructurale.Résultats :Caractérisation morphométrique : > de75% des patients ont une orientation des TSAo à ± 15° par rapport à la moyenne, et une variabilité de la distance entre les ostia TSAo de ± 4 mm.Les facteurs indépendants associés aux endofuites, défaut d’apposition et mal-positionnement sont respectivement:(1) collet proximal court; (2) angulation de la zone d’ancrage (valeur seuil 51°); et (3) indice tortuosité (valeur seuil 1.68) Caractérisation mécanique : In vivo : une grande compliance de l’aorte porcine comparé à l’homme et une rigidification en cas de DAo.In vitro : l’aorte porcine a un comportement linéaire comparé au caractère non linéaire chez l’homme. Conclusion : Ce travail montre :- le lien entre morphométrie et complications après EP, et la faisabilité d’EP standards pour la crosse.- le modèle porcin est inapproprié pour tester les EP de l’AA. - la rigidification de la paroi en cas de DAo influencera le choix des futurs EP. / Objectives: characterize (1) arch morphometry to examine criteria favoring complications after thoracic endovascular aortic repair (TEVAR) and feasibility of « off-the-shelf » fenestrated devices.(2) mechanical properties of ascending aorta (AA) in swine and humans, with and without aortic dissection.Materials and methods : Morphometric characterization : Computed tomographic angiography were analysed to calculate elementary morphometric, geometric and supra-aortic trunks data Mechanical characterization : In vivo: arterial pressure and diameters measured with echocardiophy are used to calculate elastic parameters.Ex vivo: biaxial tensile testing performed on AA plus histological and microstructural analysis. Results :Morphometric characterization : In > 75% of cases supra-aortic branches are positioned within 15° of each other and distances between them have a variability of ± 4 mm.Independant factors associated with endoleak, bird beak and mis-positioning are respectively : (1) short proximal neck (2) landing zone angulation (cut-off value: 51°); and (3) tortuosity index (cut-off value: 1.68). Mechanical characterization : in vivo: greater compliance of swine aorta compared to humans and a stiffer aorta in case of aortic dissectionBiaxial testing: linear stress-strain behavior of swine aorta, compared to a non linear one in human. Conclusion : our study reveals :- the impact of anatomy on complications occurrence after TEVAR, and suitable arguments for « off-the-shelf » fenestrated devices.- swine model is inappropriate to test AA dedicated stent-graft.- stiffer wall in aortic dissection has consequences on the choice of futur devices dedicated to AA.

Η νευρολογικές διαταραχές και κυρίως η παραπληγία, αποτελούν τις πιο καταστροφικές επιπλοκές των επεμβάσεων στη θωρακο-κοιλιακή αορτή. Η διαδικασία ισχαιμίας/επαναιμάτωσης κατά τις επεμβάσεις αυτές λόγω του αποκλεισμού της αορτής, προκαλεί την ανάπτυξη τοξικών ελεύθερων ριζών οξυγόνου φαινόμενο που ορίζει το οξειδωτικό stress. Ο σκοπός της παρούσας μελέτης είναι ο καθορισμός και η ανίχνευση των ελευθέρων ριζών, αλλά και η επίδραση της Αμιφοστίνης, ενός αντιοξειδωτικού παράγοντα της κατηγορίας των θειολών. Μέθοδος: Η μέθοδος αφορά δεκαοκτώ αρσενικούς κονίκλους που υποβάλλονται σε ισχαιμία του νωτιαίου μυελού με αποκλεισμό της αορτής με τη χρήση ενδο-αορτικού ασκού. Ο ασκός προωθείται μέσω της μηριαίας αρτηρίας σε επίπεδο αμέσως κάτωθεν της αριστεράς υποκλειδίου αρτηρίας. Τα ζώα αποτελούσαν τρείς ομάδες. Η Ομάδα Ι αποτέλεσε την ομάδα ελέγχου. Στην Ομάδα ΙΙ η αορτή αποκλείσθηκε για 30΄και ακολούθησε επαναιμάτωση για 75΄. Στην Ομάδα ΙΙΙ χορηγήθηκε Αμιφοστίνη μέσω του καθετήρα αποκλεισμού κατά το δεύτερο ήμισυ της περιόδου αποκλεισμού (των 30΄). Στο τέλος της επαναιμάτωσης δείγματα νωτιαίου μυελού υποβλήθηκαν σε ανάλογη επεξεργασία για την ανίχνευση ελευθέρων ριζών οξυγόνου με τη χρήση υδροεθιδίνης και παραγώγων λιπιδικής υπεροξείδωσης με ιδιαίτερα ευαίσθητη μέθοδο φθορισμού. Αποτελέσματα: Τα αποτελέσματα των μετρήσεων έδειξαν αύξηση του υπεροξειδίου του οξυγόνου στην Ομάδα ΙΙ κατά 27.43% σχετικά με την Ομάδα Ι για να ακολουθήσει μείωση στην Ομάδα ΙΙΙ κατά 42.55% σε σχέση με την Ομάδα ΙΙ και κατά 15.25% από την Ομάδα ΙΙΙ. Η μέτρηση ενώσεων λιπιδικής υπεροξείδωσης που αντιδρούν με θειοβαρβιτουρικό οξύ (TBARSassay) έδειξε αύξηση κατά 55.3% στην Ομάδα ΙΙ σε σχέση με την Ομάδα Ι και μείωση κατά 30.3% στην Ομάδα ΙΙΙ σε σχέση με την Ομάδα ΙΙ. Η στατιστική ανάλυση και των δύο μεθόδων ανέδειξε σημαντική διαφορά με ( p<0.05). Συμπεράσματα: Ο αποκλεισμός της κατιούσας αορτής σε επίπεδο αμέσως κάτωθεν της αριστεράς υποκλειδίου αρτηρίας, προκαλεί αναμφισβήτητα ισχαιμία του νωτιαίου μυελού. Η ανάπτυξη οξειδωτικού stressως αποτέλεσμα της διαδικασίας ισχαιμία/επαναιμάτωση ανιχνεύεται μέσω των ριζών υπεροξειδίου και παραγώγων λιπιδικής υπεροξείδωσης. Η έγχυση Αμιφοστίνης προτείνεται ως αντιοξειδωτικός παράγων που μπορεί να ανιχνεύσει και να δεσμεύσει τις ελεύθερες ρίζες οξυγόνου κατά το οξειδωτικό stress που προκαλεί η ισχαιμία /επαναιμάτωση του νωτιαίου μυελού. / Paraplegia is the most devastating complication of thoraco-abdominal aortic procedures. An ischemia-reperfusion procedure is known to elevate free radicals causing oxidative stress. The aim of this study is to determine and to detect the free radical products and to examine the influence of Amifostine, a triphosphate agent, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods: Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by inflation of a coronary artery balloon catheter, advanced to descending thoracic aorta through the femoral artery. The animals were randomly divided into 3 groups. Group I functioned as control. In group II the aorta was occluded for 30 minutes and then re-perfused for 75 min. In group III, 500mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay. Results: Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64±0.10), in group II between 1.96 and 2.50 (2.10±0.21), and in group III (amifostine) between 1.21 and 1.60 (1.40±0.13) (p=0.00), showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.28 and 0.31 (0.30±0.01), in group II between 0.427 and 0.497 (0.466±0.024), and in group III (amifostine) between 0.343 and 0.357 (0.36±0.005) (p<0.00), showing a decrease of 38% after Amifostine administration. Conclusions: Occlusion of aorta below left subclavian artery causes spinal cause ischemia without the interference of collateral perfusion. Modified use of hydrο-ethidine is a useful assay for the detection of superoxide radicals. By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion significantly attenuated the spinal cord oxidative injury.

Vasorrelaxant effects of R(+)-pulegone were tested in normotensive rats using two different methodological approaches. In vivo, increasing doses (1, 3, 10, 20 and 30 mg / kg) were administered in the animals, i.v. bolus and selected randomly, then the parameters for mean arterial pressure (MAP) and heart rate (HR) were evaluated. In this situation the substance triggered a hypotensive effect and bradycardia. In the ex vivo approach, we used the thoracic aorta of these animals and isometric tension experiments, evaluated the vasorelaxant activity of the substance. The administration of R (+)-pulegone triggered vasorelaxant effect concentration-dependent in both rings with intact endothelium and with this removed, but the substance had the lowest pD2 value in the presence of the endothelium (-3.64 ± 0.06, n = -3.17 vs 5 ± 0.034, n = 6, respectively), no change in peak effect (98.2 ± 1.2%, n = 5 vs. 106.0 ± 8.1%, n = 6) indicating that the substance acts triggering vasodilation in aortic dependent manner and independent of the vascular endothelium. In rings with intact endothelium, the vasorelaxant activity of R(+)-pulegone was not altered in the presence of diclofenac and atropine, but was modified by L-NAME (-3.00 ± 0.016; n=5), HDX (-3.07 ± 0.021; n=5), ODQ (-3.17 ± 0.03; n = 5) and the red ruthenium (-3.14 ± 0.04; n=5) vs control: -3.64 ± 0.06; n = 5. These results suggest that the substance is probably stimulating NO production via the activation of TRP channels. In smooth muscle vascular, R(+)-pulegone inhibited curve calcium concentration-dependent manner (Emax: 10-4 M: 68 9 ± 3.81%; 3x10-4 M: 40.97 ± 8.05%; 10-3 M: 24.79 ± 5.04% and 3x10-3 M: 0.29 ± 0.33%) via calcium channels type L, as in the presence of nifedipine, there was a reduction of the maximum effect (Emax: 93.3 ± 1.7% ; n = 6 vs Emax control: 106.8 ± 8.1%; n = 6 ). Additionally, it was surveyed the participation of for potassium channels, using 4-aminiopiridine, it was seen that the substance has inhibited response by blocking the potassium channels sensitive to voltage (-2.93 ± 0.012 - n = 5 vs control - 3.17 ± 0.034 - n = 6) as well as sensitive to ATP, since, in the presence of glybenclamide, the relaxant response to R(+)-pulegone was also inhibited (-2.94 vs. -3.17 ± 0.012 ± 0.03). Thus, to cause vasorelaxation in normotensive rat thoracic aorta, R(+)-pulegone, stimulates the production of NO in endothelial cells, probably by activating calcium influx via TRP channels. The effect independent of the endothelium is mediated by inhibition of calcium influx, likely through the CaV and for opening potassium channels (KATP and Kv). / O efeito vasorrelaxante de R(+)-pulegona foi estudado em ratos normotensos, utilizando duas abordagens metodológicas. Na avaliação in vivo, doses crescentes (1, 3, 10, 20 e 30 mg/Kg), foram administradas nos animais, via i.v. em bolus de maneira aleatória, posteriormente os parâmetros de pressão arterial média (PAM) e frequência cardíaca (FC) foram avaliados. Nesta situação a substância desencadeou um efeito hipotensor e bradicárdico dependente de dose. Na abordagem ex vivo, utilizou-se a aorta torácica destes animais e avaliou-se a atividade vasorrelaxante da substância. A administração de R(+)-pulegona desencadeou efeito vasorrelaxante, concentração dependente tanto em anéis com endotélio intacto quanto com este removido, porém a substância apresentou o valor do pD2 menor na presença do endotélio (-3,64 ± 0,06, n=5 vs -3,17 ± 0,034, n=6, respectivamente), sem nenhuma alteração no efeito máximo (98,2 ± 1,2%, n=5 vs 106,0 ± 8,1%, n=6), indicando que a substância atua desencadeando vasodilatação na aorta de maneira dependente e independente do endotélio vascular. Em anéis com endotélio intacto, a atividade vasorrelaxante de R(+)-pulegona não foi alterada na presença de diclofenaco e atropina, porém foi modificada por L-NAME (-3,00 ± 0,016, n=5), HDX (-3,07 ± 0,021, n=5), ODQ (-3,17 ± 0,03, n=5) e o vermelho de rutênio (-3,14 ± 0,04, n=5) todos vs controle: -3,64 ± 0,06, n=5. Estes resultados sugerem que a substância provavelmente está estimulando a produção de óxido nítrico (NO), via ativação dos canais TRP na célula endotelial. O efeito dependente do músculo liso vascular de R(+)-pulegona dá-se através da inibição da curva de cálcio de maneira dependente de concentração (Emáx: 10-4 M: 68,9 ± 3,81%; 3x10-4 M: 40,97 ± 8,05%; 10-3 M: 24,79 ± 5,04% e 3x10-3 M: 0,29 ± 0,33%), via canais para cálcio tipo L, pois na presença de NIF, ocorreu redução do efeito máximo (Emáx: 93,3 ± 1,7%, n= 6 vs controle Emáx: 106,8 ± 8,1%, n=6). Adicionalmente, pesquisou-se a participação dos canais para potássio e na presença de 4-AP ocorreu redução da resposta relaxante da substância indicando a participação dos canais para potássio sensíveis a voltagem (-2,93 ± 0,012, n=5 vs controle -3,17 ±0,034, n=6) e também sensíveis ao ATP, uma vez que, na presença de glibenclamida, a resposta relaxante para R(+)-pulegona também foi reduzida (-2,94 ± 0,012, n=5 vs -3,17 ± 0,03, n=6). Assim, para causar vasorrelaxamento em aorta torácica de ratos normotensos, R(+)-pulegona, estimula a produção de NO na célula endotelial, provavelmente por ativar o influxo de cálcio via canais TRP e o efeito independente do endotélio, é mediado pela inibição do influxo de cálcio, provavelmente através dos CaV e abertura dos canais para potássio (Kv e KATP).

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.