Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2018-03-26T14:34:13Z No. of bitstreams: 1 2015 - Fernando de Azevedo da Cruz Seara.pdf: 1716878 bytes, checksum: 6a6ea74b23b441a8aafb15e937dea036 (MD5) / Made available in DSpace on 2018-03-26T14:34:14Z (GMT). No. of bitstreams: 1 2015 - Fernando de Azevedo da Cruz Seara.pdf: 1716878 bytes, checksum: 6a6ea74b23b441a8aafb15e937dea036 (MD5) Previous issue date: 2015-07-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / According to World Health Organization, ischemia heart diseases are the leading cause of death worldwide. Among therapeutic approaches, reperfusion is the most effective and indicated is reperfusion. Despite the better post-infarction prognostic, absolute improvement on cardiac function is hardly achieved due to ischemia/reperfusion injury (IRI). Within this context, anabolic steroids (AS) administration, in adult Wistar rats, significantly increase IRI susceptibility. Moreover, chronic administration of AS, during adolescent phase, induces persistent cardiovascular dysfunctions along adulthood. Therefore, the aim of the present study was to analyze the effects of chronic administration of supraphysiologic doses of testosterone propionate, during adolescent phase, in the susceptibility to ischemia/reperfusion injury, in adult Wistar rats. To perform it, 24 Wistar rats were allocated into two groups, AS (Testosterone propionate 5 mg kg-1, since 26? day postnatal, 5 days per week, during 5 weeks) and Control (Vehicle). In the 82? postnatal, rats were euthanized and hearts, livers, lungs, kidneys and testicles were collected. Isolated hearts were artificially perfused with modified Krebs-Henseleit solution, through Langendorff apparatus, and, then, submitted to ex vivo ischemia ? reperfusion protocol (20 minutes of stabilization, 30 minutes of global ischemia and 60 minutes of reperfusion). The left ventricle (LV) end diastolic- LVEDP), systolic- (LVSP) and developed pressures (LVDP), as well as first derivatives of pressure, maximum and minimum (dP/dt, maximum and minimum, respectively) were measured through an intraventricular latex balloon, connected to a pressure transducer. Through the electrocardiogram, susceptibility to arrhythmic episodes was analyzed. At the end of the protocol, area of infarct was delimited and gene expression of ? and ? myosin heavy chains and Glyceraldehyde 3-phosphate dehydrogenase, as well as the activity of nicotinamide adenine dinucleotide phosphate-oxidase (Nox) enzymes, were calculated. In comparison to Control group, hearts from AS group presented: Hypertrophy, due to an increase in cardiac mass (33%, P<0,001) and index (37%, P<0,001); Significantly increase in the area of infarct (54,76%, P<0,05); Worst recovery of both LVEDP and LVDP, along reperfusion; Less recovery of maximum dP/dt, during reperfusion, despite the equivalent LVSP; Reduced basal minimum dP/dt and, subsequently, reduction in the recovery of the aforementioned parameter, regarding reperfusion period; Enhanced gene expression of MHC? (%), consistent with the loss of mechanical performance; Increased incidence of arrhythmic episodes in the reperfusion period (100%, P<0,01). No statistical difference could be seen in regard to the Nox activity. For the first time, we demonstrated that AS treatment during adolescent phase promotes cardiac hypertrophy and gene reprogramming, both persistent during adulthood, besides an increase susceptibility to IRI, through in the larger area of infarct and poor recovery of cardiac electrical and mechanical proprieties, in isolated hearts of adult Wistar rats / De acordo com a OMS, as doen?as isqu?micas do cora??o consistem na maior causa mortis global. Dentre as abordagens terap?uticas, a mais eficaz ? a reperfus?o. A despeito da melhora no progn?stico p?s-infarto, a recupera??o plena da fun??o card?aca dificilmente ? alcan?ada, devido a inj?ria de isquemia/reperfus?o (IIR). Neste contexto, a administra??o de EA em ratos Wistar adultos enaltece a susceptibilidade ? IIR. Ademais, a administra??o de EA em ratos Wistar, ao longo da adolesc?ncia, favorece o desenvolvimento de disfun??es cardiovasculares persistentes durante a fase adulta. Desta forma, objetivou-se, com o presente estudo, analisar os efeitos da sobrecarga cr?nica de propionato de testosterona, ao longo da fase adolescente, na susceptibilidade ? IIR, em ratos Wistar adultos. Para tanto, foram utilizados 24 ratos Wistar machos, divididos em dois grupos: EA (Propionato de testosterona 5 mg kg-1, a partir do 26? dia p?s-natal, 5 vezes por semana/ 5 semanas) e CTL (ve?culo). No 82? dia p?s-natal, os ratos foram submetidos ? eutan?sia para a coleta ?rg?os. Os cora??es isolados foram submetidos ? perfus?o artificial em aparato de Langendorff, e, assim, ao protocolo de isquemia/reperfus?o. As press?es diast?lica final (PDF), sist?lica (PS) e desenvolvida (PD), do ventr?culo esquerdo (VE), e as primeiras derivadas de press?o do VE, m?xima e m?nima (dP/dt m?xima e m?nima, respectivamente), foram mensuradas atrav?s de um bal?o de l?tex intraventricular, conectado a um transdutor de press?o. Atrav?s do eletrocardiograma, foi analisada a susceptibilidade aos epis?dios arr?tmicos. Ao final do protocolo, as ?reas de infarto foram demarcadas e a express?o g?nica das cadeias pesadas de miosina e gliceralde?do-3-fosfato desidrogenase, assim como a atividade enzimas da fam?lia de niconinam?da adenina dinucleot?deo fosfato oxidase (Nox), no ventr?culo esquerdo, foram avaliadas. Em rela??o ao grupo Controle, os cora??es dos animais tratados com EA apresentaram: Hipertrofia, atrav?s do aumento na massa (aumento de 33%, P<0,001) e do ?ndice card?aco (aumento de 37%, P<0,001); aumento significativo da ?rea de infarto (aumento de 54,76%, P<0,05); T?nue recupera??o da PDFVE, assim como da PDVE, durante a reperfus?o; Inferior recupera??o da dP/dt m?xima, ao longo da reperfus?o, a despeito da equivalente recupera??o na PSVE; Reduzida dP/dt m?nima basal e, subsequentemente, redu??o na recupera??o deste par?metro, ao longo da reperfus?o; Aumento significativo da express?o g?nica da MHC? (P<0,01), condizente o preju?zo no desempenho mec?nico; Maior incid?ncia de epis?dios arr?tmicos, ao longo da reperfus?o (aumento de 100%, P<0,01). N?o houve diferen?a em rela??o ?s atividades das Nox. Pela primeira vez, foi demonstrado que a administra??o de EA, ao longo da adolesc?ncia, provoca hipertrofia e reprograma??o g?nica card?aca, persistente durante a fase adulta, al?m de aumentar, significativamente, a susceptibilidade ? IIR, por meio do aumento na ?rea de infarto e piora na recupera??o das propriedades mec?nicas e el?tricas card?acas, em cora??es isolados de ratos Wistar adultos.