Turbulent flow downstream of a bileaflet mechanical heart valve is investigated using digital particle image velocimetry. Evolution of flow structures during the systole and diastole phases of a typical cardiac cycle is characterized by obtaining global flow velocity measurements in multiple cross-sections of the flow field. Instantaneous and time-averaged patterns of flow velocity, vorticity, and streamline topology are used to illustrate the interaction between the unsteady vortices that results in elevation of shear stress levels. This image-based approach can potentially lead to development of methods of control of platelet activation and provides insight into the underlying flow physics.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [197]-225).

Thesis (M. S.)--Chemical and Biomolecular Engineering, Georgia Institute of Technology, 2005. / Dr. Athanassios Sambanis, Committee Member ; Dr. Timothy M. Wick, Committee Member ; Dr. Ajit P.Yoganathan, Committee Chair. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2005. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 Aug 15.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Description based on contents viewed June 24, 2007; title from title screen. Includes bibliographical references (p. 76-80).

Η εκφυλιστική στένωση της αορτικής βαλβίδας και τα οξέα στεφανιαία σύνδρομα αποτελούν τις σημαντικότερες αιτίες θανάτου από καρδιαγγειακά νοσήματα. Είναι τεκμηριωμένο ότι ο ρόλος της ασβεστοποίησης στην παθοφυσιολογία των ανωτέρω νοσημάτων είναι σημαντικός και αναμφισβήτητος. Μέχρι πρόσφατα θεωρούταν ότι η ασβεστοποίηση αποτελεί παθητική διαδικασία εναπόθεσης αλάτων ασβεστίου σε ιστούς που έχουν υποστεί κάποιου βαθμού βλάβη. Ωστόσο τελευταία δεδομένα υποδεικνύουν ότι πρόκειται για ενορχηστρωμένη διαδικασία που έχει ως αποτέλεσμα την κυτταρική διαφοροποίηση και την ενεργοποίηση μεταγραφικών παραγόντων που σχετίζονται με τον οστίτη ιστό. Προκειμένου να τεκμηριώσουμε την άποψη ότι η ασβεστοποίηση των αορτικών βαλβίδων και στεφανιαίων αρτηριών στηρίζεται σε μία ενεργό διαδικασία που περιλαμβάνει την ενεργοποίηση χονδρο – οστεογενών οδών, μελετήσαμε ανοσοϊστοχημικά για πρώτη φορά την έκφραση των παραγόντων NFATc1 και Osterix. Επιπρόσθετα, διερευνήσαμε άλλα χαρακτηριστικά του προγράμματος οστεογενούς και χονδρογενούς διαφοροποίησης όπως την έκφραση των παραγόντων OPG, RANKL, RANK, Runx2 και Sox9 καθώς και τη συμμετοχή της φλεγμονής, της νεοαγγείωσης και της υπερπλασίας κυττάρων που εκφράζουν α - SMA. Στην παρούσα ερευνητική εργασία τεκμηριώνεται για πρώτη φορά η συμμετοχή των βασικών ρυθμιστικών παραγόντων των οστών NFATc1 και Osterix στη διαδικασία ασβεστοποίησης των αορτικών βαλβίδων και των στεφανιαίων αρτηριών στον άνθρωπο. Επιπρόσθετα, επιβεβαιώνεται η συμβολή των παραγόντων Runx2 και Sox9 στη δημιουργία αποτιτανώσεων στους συγκεκριμένους ιστούς. Οι αλλαγές στην έκφραση του συμπλέγματος OPG/RANKL/RANK σχετίζονται με την ασβεστοποίηση της αορτικής βαλβίδας. Αντίθετα, το προφίλ έκφρασης του συμπλέγματος δεν είναι σταθερό στις στεφανιαίες αρτηρίες επιβεβαιώνοντας αντικρουόμενα αποτελέσματα προηγούμενων μελετών. Τέλος, επιβεβαιώνεται η συμμετοχή της φλεγμονής, της νεοαγγείωσης και της υπερπλασίας των κυττάρων με συσταλτικό φαινότυπο στην εξέλιξη της παθοφυσιολογικής διεργασίας. Από την παρούσα μελέτη διαπιστώνουμε ότι η διαδικασία της ασβεστοποίησης στις αορτικές βαλβίδες και τις στεφανιαίες αρτηρίες παρουσιάζει αρκετές ομοιότητες με την οστεογένεση. Αυτό συνεπάγεται ευοίωνες προοπτικές για δυνητική γονιδιακή παρέμβαση σε πρώιμα στάδια που θα μπορούσε να οδηγήσει σε αναστροφή της παθοφυσιολογικής διαδικασίας εναπόθεσης ασβεστίου. / Degenerative aortic stenosis and acute coronary syndromes constitute major causes of cardiovascular morbidity. There is evidence that calcification plays significant role in pathophysiology of these diseases. Until recently, calcification was considered to be a passive process of calcium deposition in injured tissue. However, recent data suggest that calcification of aortic valves and coronary arteries is an active process related to cellular differentiation and transcription of bone regulators. In order to provide further evidence that aortic valve and coronary artery calcification is an active process involving chondro-osteogenic pathways, we investigated using immunohistochemistry the expression of NFATc1 and Osterix in human calcified aortic valves and coronary arteries, which to the best of our knowledge has not been reported previously. Additionally, we investigated in our specimens other features of chondro/osteogenic differentiation program such as the expression of OPG, RANKL, RANK, Runx2 and Sox9, and the participation of inflammation, neovessel formation and hyperplasia of α - SMA positive cells in calcification process. Our results provide evidence for the involvement of bone regulatory factors NFATc1 and Osterix in aortic valve and coronary artery calcification process in human. In addition, we confirm Runx2 and Sox9 expression in diseased specimens. Expression pattern of OPG / RANKL / RANK system is related to aortic valve calcification. Consistently with previous reports, the role of OPG / RANKL / RANK system in coronary artery calcification is not clear. Finally, our study confirms involvement of inflammation, neovessel formation and hyperplasia of α - SMA positive cells in calcification process. Present study demonstrates that aortic valve and coronary artery calcification is actually an active process sharing features with developmental osteogenesis. This fact implies promising prospects for potential genetic intervention in early stages that could lead to inhibition of calcification process.

Η ασβέστωση της αορτικής βαλβίδας σχετίζεται με αυξημένη νοσηρότητα και θνητότητα, ιδιαίτερα στους ηλικιωμένους. Μέχρι σήμερα η φαρμακευτική θεραπεία δεν έχει αποδειχθεί τόσο αποτελεσματική, όσο η χειρουργική. Στην παρούσα εργασία χρησιμοποιήθηκε μοντέλο υπερλιπιδαιμικών κονίκλων προκειμένου να μελετηθεί η επίδραση του εκλεκτικού ανταγωνισμού της αλδοστερόνης στα πρώιμα στάδια της ασβέστωσης της αορτικής βαλβίδας. Αυτή η φαρμακευτική προσέγγιση δεν είχε προηγουμένως διερευνηθεί. Σαράντα αρσενικοί κόνικλοι τύπου Νέας Ζηλανδίας παρέμειναν για 4 εβδομάδες σε κανονική διατροφή και στη συνέχεια χωρίστηκαν σε 3 ομάδες: (1) ομάδα ελέγχου (control) που αποτελούνταν από 10 πειραματόζωα και συνέχισαν να τρέφονται με κανονική διατροφή για 8 εβδομάδες ακόμη, (2) ομάδα vehicle που αποτελούνταν από 15 πειραματόζωα και συνέχισαν να τρέφονται με υπερλιπιδαιμική διατροφή (1% χοληστερόλη) για 8 εβδομάδες ακόμη συν ένα διάλυμα γλυκόζης 5% (vehicle), για τις τελευταίες 4 εβδομάδες και (3) ομάδα επλερενόνης που αποτελούνταν από 15 πειραματόζωα και συνέχισαν να τρέφονται με υπερλιπιδαιμική διατροφή για 8 εβδομάδες ακόμη και τουs χορηγούνταν επλερενόνη 100 mg/kgr/day σε διάλυμα γλυκόζης 5%, για τις τελευταίες 4 εβδομάδες. Πριν από τη θυσία κάθε πειραματοζώου γινόταν μέτρηση της αρτηριακής πίεσης καθώς και των επιπέδων καλίου, ολικής χοληστερόλης και αλδοστερόνης στο πλάσμα. Μετά τις 8 εβδομάδες όλα τα πειραματόζωα θυσιάστηκαν και οι παρασκευασμένες αορτικές βαλβίδες εξετάσθηκαν με χρώση αιματοξυλίνης – ηωσίνης και Von Kossa silver stain και με ανοσοχρώσεις για τους υποδοχείς των αλατοκορτικοειδών (αλδοστερόνης), τα μακροφάγα και το μετατρεπτικό ένζυμο της αγγειοτενσίνης. Η παρουσία εναποθέσεων ασβεστίου επιβεβαιώθηκε με ηλεκτρονικό μικροσκόπιο σάρωσης. Η επλερενόνη αύξησε τα επίπεδα αλδοστερόνης στο πλάσμα, αλλά δεν επηρέασε την αρτηριακή πίεση και τα επίπεδα χοληστερόλης και καλίου. Η υπερλιπιδαιμία προκάλεσε συνάθροιση μακροφάγων και αύξηση της έκφρασης του μετατρεπτικού ενζύμου, όπως επίσης και μικροσκοπική εναπόθεση ασβεστίου στις γλωχίνες. Όλοι αυτοί οι δείκτες ελαττώθηκαν με τη χορήγηση της επλερενόνης. Η ανοσοϊστοχημία για τους υποδοχείς των αλατοκορτικοειδών ανέδειξε παρόμοια έκφραση στις γλωχίνες της ομάδας ελέγχου και της υπερλιπιδαιμικής ομάδας (vehicle). Συμπερασματικά τα αποτελέσματα αυτά δείχνουν πως οι υποδοχείς της αλδοστερόνης εκφράζονται στην αορτική βαλβίδα και πως η εκλεκτική αναστολή τους με τη χορήγηση της επλερενόνης αναστέλλει το σχηματισμό των σκληρυντικών αλλοιώσεων που προκαλούνται από την υπερλιπιδαιμική διατροφή. / Calcific aortic valve disease is associated with increased morbidity and mortality, especially in the elderly. To date, pharmacological therapies have not proven as effective as surgical intervention. Here, we used a hyperlipidemic rabbit model to investigate the potential effects of selective aldosterone inhibition on the early stages of aortic valve calcification, a pharmacological strategy that has not yet been tested. Forty New Zealand male rabbits fed a standard diet for 4 weeks were separated into three groups: (1) control (n = 10), fed a standard diet; (2) vehicle (n = 15), fed a hyperlipidemic diet (cholesterol 1%) plus vehicle; and (3) eplerenone (n = 15), fed a hyperlipidemic diet plus 100 mg/kg/d eplerenone (last 4 weeks). After 8 weeks, animals were sacrificed and prepared aortic valve sections were examined with Von Kossa silver stain and by immunostaining for mineralocorticoid receptor, macrophages and angiotensin-converting enzyme. The presence of calcium deposits was confirmed by scanning electron microscopy. Eplerenone increased aldosterone levels but did not affect blood pressure, cholesterol or potassium levels. Hyperlipidemia induced macrophage accumulation and angiotensin-converting enzyme expression, as well as calcium deposition in the leaflets. All markers were decreased by eplerenone treatment. Immunohistochemistry for mineralocorticoid (aldosterone) receptors revealed similar expression in the leaflets of both control and hyperlipidemic groups. Collectively, these results indicate that aldosterone receptors are present in rabbit aortic valve leaflets and their selective blockade with eplerenone inhibits formation of the sclerotic lesions induced by a high fat diet.

Regelmäßige körperliche Aktivität verlangsamt die Progression arteriosklerotischer Läsionen, reduziert oxidativen Stress und erhöht die Bioverfügbarkeit von Stickstoffmonoxid. Von diesen Vorgängen erwartet man auch eine Verbesserung des Outcomes bei degenerativen Aortenklappenerkrankungen. Ziel der vorliegenden Arbeit war es den Effekt von körperlicher Aktivität im Sinne einer Primärprävention auf die Ausbildung einer Aortenklappensklerose, die ein frühes Stadium in der Entwicklung einer Aortenklappenstenose darstellt, mit ihrem zu Grunde liegendem Pathomechanismus zu untersuchen. Hierfür wurde das Tiermodell der LDL-Rezeptor-knockout-Maus gewählt, da bereits in Studien die regelhafte Induktion von Aortenklappensklerosen und hämodynamisch relevante Stenosen durch cholesterinreiche Nahrung gezeigt werden konnte. Für die vorliegende Studie wurden 4 Wochen alte LDL-Rezeptor-knockout-Mäuse in 4 Gruppen randomisiert: Eine Kontroll-Gruppe mit normaler Diät und bewegungsarmen Lebensstil, eine Cholesterin-Gruppe mit cholesterinreicher Ernährung und bewegungsarmen Lebensstil, eine regelmäßige Trainingsgruppe mit cholesterinreicher Ernährung und regelmäßiger körperlicher Aktivität (60 min/d, 5 Tage/Woche) und eine gelegentlichen Trainingsgruppe, mit cholesterinreicher Ernähung und körperlicher Aktivität (60 min/d, 1 Tag/Woche) für jeweils 16 Wochen. In der 20. Woche wurden histologische Untersuchungen vorgenommen, die Verdickungen der Aortenklappen in der Cholesterin-Gruppe verglichen zur Kontroll-Gruppe zeigten. Regelmäßige, jedoch keine gelegentliche körperliche Aktivität reduziert signifikant diese Verdickung der Aortenklappe. Die immunhistochemischen Untersuchungen zeigten, dass eine Cholesterin-Diät die Endothelintegrität der Aortenklappe zerstört, wohingegen sie durch regelmäßige körperliche Aktivität geschützt wird. Weiterhin zeigte sich eine Erhöhung der Serum-Myeloperoxidase, der oxidierten Low Density Lipoproteine, der in situ Superoxide, als Marker für oxidativen Stress. Es konnten erhöhte Spiegel für Mac3, als Marker für Makrophagenakkumulation, α-smooth muscle actin, als Marker für Klappenfibrose und der proosteogene Marker Alkalische Phosphatase sowie eine erhöhte Mineralisation in der Cholesterin-Gruppe nachgewiesen werden. Wohingegen die genannten Marker in der Gruppe mit regelmäßiger körperlicher Aktivität erniedrigt nachgewiesen werden konnten. Die Ergebnisse der Polymerase-Kettenreaktion ergaben eine erhöhte Expression der messenger-RNA für α-smooth muscle actin, bone morphogentic protein-2, runt- related transcription factor-2 und Alkalische Phosphatase, als Marker für Klappenfibrose und Proosteogenese in der Cholesterin-Gruppe, dagegen waren sie durch regelmäßige körperliche Aktivität erniedrigt. Darüber hinaus erhöht regelmäßige körperliche Aktivität signifikant die Spiegel von zirkulierendem Fetuin-A, als Hemmstoff der Kalzifizierung verglichen zur Cholesterin-Gruppe. Schlussfolgernd lässt sich sagen, dass regelmäßige, jedoch keine gelegentliche körperliche Aktivität einer Aortenklappensklerose im Sinne einer Primärprävention durch eine Anzahl von Mechanismen, wie dem Schutz der Endothelintegrität, der Reduktion von Inflammation und oxidativem Stress sowie der Hemmung des osteogenen Signalweges, vorbeugt.

O expressivo número de brasileiros que necessitam correção anatômica da estenose valvar aórtica acentuada e que não realizam cirurgia de substituição valvar devido ao risco proibitivo justifica a necessidade de investigação, tanto da efetividade no cenário clínico real quanto dos custos impostos ao Sistema Único de Saúde e aos planos de saúde suplementar brasileiros pela incorporação do implante transcateter de valva aórtica, que tem se demonstrado efetivo mas oneroso, internacionalmente. No primeiro artigo da tese, avaliaram-se os desfechos intra-hospitalares, a sobrevida e o reembolso pela internação hospitalar de 41 pacientes com idade média de 78,7 ± 6,3 anos, estenose valvar aórtica acentuada, com recusa cirúrgica e decisão multidisciplinar por tratamento transcateter entre outubro de 2010 e outubro de 2015. Os sujeitos foram seguidos prospectivamente por um período mediano de 15,2 (4,5 – 25,6) meses e a sobrevida estimada em 1 e 2 anos foi de 73,2% e 64,1%, respectivamente. Identificou-se que hipertensão pulmonar e revascularização miocárdica cirúrgica prévia estavam independentemente associadas à menor sobrevida. O valor mediano reembolsado pelos pacientes atendidos pelo Sistema Único de Saúde foi R$ 108.634,34 (101.051,05 – 127.255,27) e R$ 115.126,77 (94.603,21 – 132.603,01) para aqueles internados por planos de saúde suplementar ou particulares, sendo o respectivo valor mediano reembolsado pela prótese valvar de R$ 82.000,00 (82.000,00 – 95.450,00) e 84.050,00 (75.000,00 – 92.400,00) Em um grupo de 585 procedimentos de troca valvar aórtica cirúrgica em indivíduos com idade ≥ 60 anos, realizados entre janeiro de 2010 e dezembro de 2015 na mesma instituição, a mortalidade intra-hospitalar estava associada à idade e foi de 5,9% naqueles com idade entre 60 e 70 anos, 10,8% entre 70 e 80 anos e de 22,2% ≥ 80 anos. O reembolso mediano foi de R$ 14.035,96 (11.956,11 – 16.644,90) para os internados pelo Sistema único de Saúde e R$ 20.273,97 (15.358.03 – 32.815,49) pelos planos de saúde suplementar ou particulares. No segundo artigo da tese, identificou-se que do total de 819 pacientes consecutivamente incluídos no Registro Brasileiro de Implante de Bioprótese Aórtica por Cateter entre janeiro de 2008 e outubro de 2015, 15 (1,8%) sofreram perfuração do ventrículo esquerdo. Os pacientes que apresentaram perfuração eram mais idosos (85,4 ± 6,3 vs. 81,5 ± 7,3 anos, p=0,038), predominantemente mulheres (80,0% vs. 50,5%, p=0,024), apresentavam maior fração de ejeção (67,3 ± 7,8% vs. 58,6 ± 15,0%, p=0,001), menor massa ventricular esquerda (203,9 ± 47,1g vs. 247,6 ± 78,7g, p=0,039) e menor altura do tronco da coronária esquerda (11,2 ± 5,4mm vs. 14,0 ± 3,3mm, p=0,034). Os preditores independentes de perfuração do ventrículo esquerdo foram idade e fração de ejeção. No terceiro artigo, descreve-se um caso de ablação septal para tratamento de miocardiopatia hipertrófica obstrutiva assimétrica para posterior implante transcateter de valva aórtica, sugerindo que esta seja uma estratégia factível quando da concomitância dessas duas condições Em conclusão, os desfechos do tratamento transcateter da estenose valvar aórtica acentuada em pacientes inoperáveis são compatíveis com aqueles do cenário idealizado dos ensaios clínicos randomizados, apesar de estarem associados a custos maiores que os anteriormente estimados por painéis de especialistas. O tratamento cirúrgico, por sua vez, apresentou mortalidade maior que aquela idealizada ou relatada como usual. A hipercinesia do ventrículo esquerdo pode favorecer o trauma determinado pelo guia metálico, posicionado em seu interior para realização do procedimento, estando a fração de ejeção independentemente associada à chance de perfuração. Ainda, a ablação septal por álcool eletiva, anterior ao implante transcateter da valva aórtica, é uma abordagem factível para pacientes com hipertrofia ventricular esquerda assimétrica obstrutiva associada à estenose valvar aórtica. / The expressive number of Brazilians who require an anatomic correction for severe aortic valve stenosis and who do not undergo valvar replacement surgery due to prohibitive risk justifies the need to investigate both the effectiveness in the real clinical scenario and the costs imposed to the Public Health System and the Supplementary Health System for the incorporation of the transcatheter aortic valve implantation, which has been shown to be effective but onerous, internationally. In the first article of the thesis, the in-hospital outcomes, long-term survival and reimbursement for 41 patients, with a mean age of 78.7 ± 6.3 years, sever aortic valve stenosis, with surgical refusal and multidisciplinary decision for transcatheter treatment, between October 2010 and October 2015 are described. Subjects were prospectively followed for a median period of 15.2 (4.5 - 25.6) months and the estimated survival at 1 and 2 years was 73.2% and 64.1%, respectively. It was identified that pulmonary hypertension and previous coronary artery bypass grafting were independently associated with lower survival. Median reimbursed values by the Public Health System was R$ 108,634.34 (101,051.05 - 127,255.27) and by supplementary health plans was R$ 115,126.77 (94,603.21 - 132,603.01). The respective median values reimbursed for the valve prosthesis was R$ 82,000.00 (82,000.00 - 95,450.00) and 84,050.00 (75,000.00 - 92,400.00) In a group of 585 surgical aortic valve replacement procedures in subjects aged ≥ 60 years, performed between January 2010 and December 2015 in the same institution, in-hospital mortality was associated with age and was 5.9% in those with age between 60 and 70 years, 10.8% between 70 and 80 years and 22.2% in ≥ 80 years. The median reimbursement was R$ 14,035.96 (11,956.11 - 16,644.90) for those hospitalized by the Public Health System and R$ 20,273.97 (15,358.03 - 32,815.49) by supplementary or private health plans. In the second article of the thesis, it was identified that of the total of 819 patients consecutively included in the Brazilian Registry of Aortic Bioprosthesis Implantation by Catheter (RIBAC) between January 2008 and October 2015, 15 (1.8%) suffered perforation of the left ventricle. Patients with perforation were older (85.4 ± 6.3 vs. 81.5 ± 7.3 years, p=0.038), predominantly women (80.0% vs. 50.5%, p=0.024), had a higher ejection fraction (67.3 ± 7.8% vs. 58.6 ± 15.0%, p=0.001), lower left ventricular mass (203.9 ± 47.1g vs. 247.6 ± 78, 7g, p=0.039) and shorter distance between the aortic annulus and the left main coronary artery ostium (11.2 ± 5.4mm vs. 14.0 ± 3.3mm, p=0.034). The independent predictors of left ventricular perforation were age and ejection fraction. In the third article, a case of septal ablation was described for the treatment of asymmetric obstructive hypertrophic cardiomyopathy for posterior transcatheter aortic valve implantation, suggesting that this is a feasible strategy when these two conditions are concomitant In conclusion, the outcomes of transcatheter treatment of severe aortic stenosis in inoperable patients are compatible with those in the ideal scenario of randomized clinical trials, although they are associated with higher costs than previously estimated by expert panels. Surgical treatment, on the other hand, presented higher mortality than that idealized or reported as usual. The left ventricle hyperkinesia may favor the trauma determined by the metallic guide, positioned inside it to perform the procedure, the ejection fraction being independently associated with the chance of perforation. Furthermore, elective alcohol septal ablation, prior to transcatheter aortic valve implantation, is a feasible approach for patients with obstructive asymmetric left ventricular hypertrophy associated with aortic valve stenosis.

Made available in DSpace on 2016-06-07T17:12:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-02. Added 1 bitstream(s) on 2016-06-07T17:16:46Z : No. of bitstreams: 1 000866188.pdf: 703355 bytes, checksum: 0b29948d0caf17093c2ef18fe5f398a8 (MD5) / A insuficiência cardíaca caracteriza-se pela diminuição da capacidade física com exacerbação precoce de fadiga e dispneia. Embora alterações intrínsecas da musculatura esquelética têm sido responsabilizadas por esses sintomas, os mecanismos envolvidos nas anormalidades musculares ainda não estão completamente esclarecidos. O estresse oxidativo miocárdico e sistêmico está aumentado na insuficiência cardíaca. Entretanto, há pouca informação sobre seu papel nas alterações da musculatura esquelética e sobre as fontes de geração de espécies reativas de oxigênio (EROs). Apesar do complexo NADPH oxidase constituir importante fonte geradora de EROs, poucos estudos avaliaram seu comportamento em músculos esqueléticos durante a insuficiência cardíaca. No miocárdio, a apocinina pode inibir o complexo NADPH oxidase e reduzir o estresse oxidativo durante agressão cardíaca. Objetivo: Avaliar os efeitos do tratamento com apocinina sobre alterações cardíacas e anormalidades fenotípicas e do estresse oxidativo do músculo sóleo de ratos com insuficiência cardíaca induzida por estenose aórtica supravalvar. Métodos: Vinte semanas após a indução da estenose aórtica, ratos Wistar foram alocados nos grupos estenose aórtica (EAo), EAo tratado com apocinina (EAo-apo) e controle (Sham). A apocinina foi administrada por oito semanas na água de beber (16 mg/kg/dia). Ecocardiograma transtorácico foi realizado antes e após o tratamento com apocinina. A atividade das enzimas antioxidantes superóxido dismutase, glutationa peroxidase e catalase e a concentração de hidroperóxido de lipídeo foram avaliadas por espectrofotometria no músculo sóleo. A concentração sérica de malonaldeído, a atividade muscular da NADPH oxidase e a geração total de EROs no músculo sóleo foram analisadas por HPLC. No sóleo, a composição das cadeias pesadas de miosina foi avaliada por eletroforese e a área seccional das fibras foi... / Heart failure is characterized by a decreased functional capacity with early fatigue and dyspnea. Although intrinsic skeletal muscle changes may be at least partially responsible for these symptoms, mechanisms involved in muscle abnormalities are not completely clear. Myocardial and systemic oxidative stress is increased during heart failure. However, there is scarce information on the sources of oxygen reactive species (ROS) and on the role of oxidative stress in inducing skeletal muscle changes. NADPH oxidase complex is an important source of ROS; only a few studies have evaluated its activity in skeletal muscles during heart failure. In myocardial, apocynin can inhibit NADPH oxidase activity and reduce oxidative stress during cardiac injury. Purpose: In this study we evaluated the effects of the antioxidant apocynin on cardiac alterations and soleus muscle oxidative stress and phenotypic characteristics in rats with supravalvar aortic stenosis-induced heart failure. Methods: Twenty weeks after inducing aortic stenosis, Wistar rats were assigned into three groups: aortic stenosis (AS), AS treated with apocynin (AS-apo, 16 mg/kg/day dissolved in drinking water for eight weeks), and control (Sham). Transthoracic echocardiogram was performed before and after apocynin treatment. Activity of the antioxidant enzymes superoxide dismutase, gluthatione peroxidase, and catalase, and lipid hydroperoxide concentration were assessed by spectrophotometry in the soleus muscle. Serum concentration of malondialdehyde and soleus muscle NADPH oxidase activity and total ROS generation were analyzed by HPLC. Soleus myosin heavy chain composition was evaluated by electrophoresis and fiber cross-sectional areas were measured in hematoxylin and eosin-stained histological sections. Statistical analysis: one-way analysis of variance complemented by Bonferroni or Mann- Whitney test. Results: Before treatment, AS and AS-apo groups presented concentric hypertrophy ...