Estudio del mecanismo del precondicionamiento del miocardio inducido por ejercicio en el perro. Participación del canal de potasio mitocondrial sensible a ATP, Ión calcio y NADPH oxidasa
BACKGROUND. We previously showed that exercise induces early and late preconditioning on the myocardial infarct size in dogs, and that the early preconditioning is mediated by activation of NADPH oxidase and by mitochondrial adenosine triphosphate-sensitive potassium channels (mitoKATP). HYPOTHESES...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/401759 |
| Acceso en línea: | http://hdl.handle.net/10803/401759 |
| Access Level: | acceso abierto |
| Palabra clave: | Infart de miocardi Infarto de miocardio Myocardial infarction Calci Calcio Calcium Ciències de la Salut 616.1 |
| Sumario: | BACKGROUND. We previously showed that exercise induces early and late preconditioning on the myocardial infarct size in dogs, and that the early preconditioning is mediated by activation of NADPH oxidase and by mitochondrial adenosine triphosphate-sensitive potassium channels (mitoKATP). HYPOTHESES AND OBJECTIVES. In a first stage we studied if late preconditioning by exercise is also mediated through these mitoKATP channels. We then approached our main objective, if the increase in Ca2+ inflow to the cell during exercise triggers early and late preconditioning on the infarct size in dogs, independent of its hemodynamic effects, based on the intracoronary administration of Ca2+ induces preconditioning, and that exercise enhances the Ca2+ inflow to the cell. In parallel, we studied whether this increase in Ca2+ inflow is also responsible for the activation of NADPH oxidase during early preconditioning. METHODS. A total of 202 dogs were surgically instrumented and trained to run on a treadmill, and then randomly assigned to one of three experimental protocols: 1) effect of blocking the mitoKATP channel with 5 hydroxydecanoate (5HD) in the late preconditioning by exercise; 2) effect of blocking sarcolemmal L-type Ca2+ channel channel with a low dose of verapamil on early and late preconditioning by exercise; 3) effect of verapamil on NADPH oxidase activation in early exercise preconditioning. RESULTS. Exercise reduced myocardial infarct size by 76% and 52-56% (early and late protection respectively, P <0.05 vs control), late preconditioning was abolished by 5HD administration, and both early and late preconditioning were abolished by a single low dose of verapamil given before exercise. This dose of verapamil did not modify the effect of exercise on metabolic and hemodynamic parameters. In addition, verapamil blocked the activation of NADPH oxidase during early preconditioning. Exercise did not induce myocardial ischemia, there were no hemodynamic differences between the groups during periods of ischemia and reperfusion, and the effects were independent of the collateral flow to the ischemic region. CONCLUSIONS. Late preconditioning is mediated by mitoKATP channels, early and late preconditioning is triggered, at least in part, by Ca2+ inflow increase to the cell during exercise and, during the early protection, is mediated by NADPH oxidase activation. |
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