Remote Mechanisms of Myocardial Protection

María A. Goyeneche, Martín Donato, DIAMELA T. Páez, Mariana Garcés, Timoteo Marchini, Virginia Pérez, Martín Grinspun, Julieta del Mauro, Christian Höcht, Pablo Evelson, Ricardo J. Gelpi

Abstract


Background: Remote ischemic preconditioning (rIPC) has been suggested to reduce infarct size through the activation of a parasympatheticneural pathway. However, the intracellular mechanisms responsible for this protection remain unclear.Objective: The aim of this study was to describe some of the intracellular protective signals activated at the cardiac level by rIPCprior to myocardial ischemia.Methods: Isolated rat hearts were subjected to 30 minutes of global ischemia and 120 minutes of reperfusion (I/R). In a secondgroup, before the isolation of the heart, a rIPC protocol (three cycles of left femoral artery ischemia/reperfusion) was performed,followed by the I/R protocol. Additionally, four experimental groups were studied, in which prior to the rIPC protocol a bilateralcervical vagotomy [VS (vagal section)] was performed or atropine (muscarinic receptor blocker), L-NAME (NO synthesis inhibitor),and 5-HD (mK+ATP channel blocker) was administered, respectively. Infarct size and eNOS phosphorylation were measured in I/R,rIPC, and VS groups. Finally, mitochondrial H2O2 production was assessed.Results: Remote ischemic preconditioning significantly decreased infarct size and this effect was abolished by VS and atropine,L-NAME, and 5-HD treatments. Furthermore, rIPC increased eNOS phosphorylation and this effect was abolished by VS. Finally,rIPC increased the mitochondrial H2O2 production, and this effect was also abolished by VS.Conclusions: Remote ischemic preconditioning activates a muscarinic vagal pathway involving eNOS phosphorylation, opening ofmitochondrial mK+ATP channels, and the production of mitochondrial H2O2.

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Revista argentina de cardiología. ISSN en línea 1850-3748. Argentine journal of cardiology (English ed. Online ISSN 2314-2286) Sociedad Argentina de Cardiología. Azcuénaga 980 (C1115AAD),Ciudad Autónoma de Buenos Aires, República Argentina. Tel. (54 11) 4961-6027/8/9 Fax: 4961-6020 www.sac.org.ar revista@sac.org.ar