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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2009.tde-06042010-175143
Document
Author
Full name
Maurício Batista Paes Landim
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Chagas, Antonio Carlos Palandri (President)
Coelho, Otavio Rizzi
Faludi, André Arpad
Serrano Junior, Carlos Vicente
Tucci, Paulo José Ferreira
Title in Portuguese
A hipercolesterolemia abole o efeito cardioprotetor do pré e pós-condicionamento isquêmico em um modelo experimental de isquemia e reperfusão em ratos
Keywords in Portuguese
Cardiotônicos
Fatores de risco
Hipercolesterolemia
Óxido nítrico
Ratos
Abstract in Portuguese
O pré e pós-condicionamento isquêmico são fenômenos cardioprotetores que limitam o dano tecidual no infarto agudo do miocárdio. Seus efeitos benéficos ocorrem através da ativação de complexas vias sinalizadoras intracelulares, que têm a inibição da formação do poro de transição de permeabilidade mitocondrial como efetor final comum. A presença de fatores de risco, como a hipercolesterolemia, pode interferir nos resultados finais quando se lança mão de tais medidas cardioprotetoras. Entretanto, há na literatura achados contraditórios que não mostram interferência do colesterol elevado sobre a cardioproteção do pré-condicionamento isquêmico. No pós-condicionamento isquêmico, mais recentemente descrito, as primeiras evidências também mostram resultados conflitantes, que carecem de mais estudos. A baixa disponibilidade do óxido nítrico presente na hipercolesterolemia está associada a níveis elevados de dimetilarginina assimétrica, um inibidor da óxido nítrico sintetase, e pode ser o responsável por abolir os benefícios de ambas as medidas cardioprotetoras aqui estudadas. Procuramos, neste trabalho, avaliar a influência da hipercolesterolemia sobre o pré e pós-condicionamento isquêmico, e correlacionar os níveis de colesterol total e dimetilarginina assimétrica com o tamanho do infarto do miocárdio experimental em ratos anestesiados. Nós encontramos um maior tamanho do infarto nos animais hipercolesterolêmicos apesar do uso destas medidas cardioprotetoras.
Title in English
Hypercholesterolemia abolishes the cardioprotective effect of ischemic pre and postconditioning in an experimental model of ischemia and reperfusion in rats
Keywords in English
Cardiotonics
Hypercholesterolemia
Nitric oxide
Rats
Risk factors
Abstract in English
Ischemic pre and postconditioning are cardioprotective phenomena that limit heart tissue damage in acute myocardial infarction. Its beneficial effects occur through the activation of complex intracellular signaling pathways, which have the inhibition of the formation of the mitochondria permeability transition pore as common final effector. The presence of risk factors such as hypercholesterolemia may interfere with final results when it makes use of such cardioprotective measures. However, there are contradictory findings in the literature which show no interference of high cholesterol on cardioprotection of ischemic preconditioning. In ischemic postconditioning, more recently described, the initial evidences also shows conflicting results, which require further studies. The low availability of nitric oxide present in hypercholesterolemia is associated with high levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, and may be responsible for removing the benefits of both cardioprotective measures studied here. The objective of our study was to assess the effect of hypercholesterolemia on ischemic pre and postconditioning and correlate the levels of total cholesterol and asymmetric dimethylarginine with the size of experimental myocardial infarction in anesthetized rats. We found a larger myocardial infarction in the hypercholesterolemic animals despite the use of these cardioprotective measures.
 
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Publishing Date
2010-04-07
 
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